Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00079274
Collaborator
Eastern Cooperative Oncology Group (Other)
3,397
894
7
105
3.8
0
Study Details
Study Description
Brief Summary
This randomized phase III trial was originally designed to compare three different combination chemotherapy regimens to see how well they work. As of September 1, 2004, the study was expanded to a total of 6 arms (the original 3 arms (A, B, C) and 3 additional arms which were the same as the first 3 but with cetuximab) in treating patients who have undergone surgery for stage III colon cancer. Drugs used in chemotherapy, such as irinotecan hydrochloride, fluorouracil, leucovorin calcium, and oxaliplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as cetuximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining more than one chemotherapy drug with monoclonal antibody therapy and giving them after surgery may kill any remaining tumor cells. It was not known at the time this study was developed which combination chemotherapy regimen is more effective after surgery in treating colon cancer. This study had several key changes, based on the results of other phase III trials. As of 6/1/2005, patients no longer received irinotecan on this study and treatment arms B, C, E, and F were discontinued. Patients on arms B and C crossed to arm A. Patients on arms E and F crossed to arm D. Patients on arms C and F who had not gotten to irinotecan continued on arms A and D, respectively. As of 8/18/2008, pre-screening for Kirsten rat sarcoma (KRAS) status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D. Patients on arm G were treated per physician discretion and followed for disease and survival status. KRAS was determined in a central laboratory and was process for all patients on this study. The primary endpoint of this study was modified on 8/18/2008 to focus on patients having wild-type KRAS tumors. All modifications were approved by the Central Institution Review Board, local Institutional Review Boards, NCI, and the NCCTG Data Safety Monitoring Board.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
PRIMARY OBJECTIVES:
- Disease-free Survival (Arms A and D: Wild-type KRAS Patients)
SECONDARY OBJECTIVES:
- Disease-free Survival (Arms A and D: Mutant KRAS Patients) II. Disease-free Survival III. Overall Survival IV. Toxicity
OUTLINE: This is a randomized, multicenter study. Patients are stratified according to positive lymph node involvement (1-3 vs 4 or more), histology (high [poorly differentiated or undifferentiated] vs low [well to moderately differentiated]), and clinical T stage (T1 or T2 vs T3 vs T4). Patients are randomized to 1 of 6 treatment arms (as of 6/1/2005, patients are randomized to treatment arms I and IV only; arms II, III, V, and VI are closed to accrual). As of 8/18/2008, pre-screening for KRAS status was added with mutant KRAS (or KRAS not evaluable) patients put on arm G and wild-type KRAS patients randomized between arm A and arm D.
ARM A: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
ARM B (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive irinotecan hydrochloride IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
ARM C (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm I for remainder of therapy): Patients receive the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease.
ARM D: Patients receive cetuximab* IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
ARM E (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm D for remainder of therapy): Patients receive cetuximab* as in arm D and irinotecan hydrochloride, leucovorin calcium, and fluorouracil as in arm B. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease.
ARM F (closed to accrual as of 6/1/2005--currently enrolled patients may cross over to arm D for remainder of therapy): Patients receive cetuximab* as in arm D and chemotherapy as in arm C.
ARM G (added as of 8/18/2008, mutant KRAS (or KRAS not evaluable) patients): Locally directed therapy.
NOTE: *Cetuximab is administered over 2 hours at a higher dose on day 1 of course 1 only.
Quality of life (QOL) is assessed at baseline, 3 months, and at the end of therapy. As of 8/18/2008, QOL was discontinued.
Patients are followed for a maximum of 8 years from randomization.
Study Design
Study Type:
Interventional
Actual Enrollment
:
3397 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase III Trial of Oxaliplatin (OXAL) Plus 5-Fluorouracil (5-FU)/Leucovorin (CF) With or Without Cetuximab (C225) After Curative Resection for Patients With Stage III Colon Cancer
Study Start Date
:
Feb 1, 2004
Actual Primary Completion Date
:
Nov 1, 2012
Actual Study Completion Date
:
Nov 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm A (combination chemotherapy) Patients received oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. |
Drug: oxaliplatin
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
| Experimental: Arm B (combination chemotherapy) Patients received irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. |
Drug: irinotecan hydrochloride
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
| Experimental: Arm C (combination chemotherapy) Patients received the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease. |
Drug: irinotecan hydrochloride
Given IV
Other Names:
Drug: oxaliplatin
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
|
| Experimental: Arm D (combination chemotherapy, monoclonal antibody) Patients received cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. |
Drug: oxaliplatin
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Biological: cetuximab
Given IV
Other Names:
|
| Experimental: Arm E (combination chemotherapy, monoclonal antibody) Patients received cetuximab as in arm D and irinotecan, leucovorin calcium, and fluorouracil as in arm B. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. |
Drug: irinotecan hydrochloride
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Biological: cetuximab
Given IV
Other Names:
|
| Experimental: Arm F (combination chemotherapy, monoclonal antibody) Patients received cetuximab as in arm D and chemotherapy as in arm C. |
Drug: irinotecan hydrochloride
Given IV
Other Names:
Drug: oxaliplatin
Given IV
Other Names:
Drug: leucovorin calcium
Given IV
Other Names:
Drug: fluorouracil
Given IV
Other Names:
Biological: cetuximab
Given IV
Other Names:
|
| Other: Arm G (Locally directed therapy) Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists. |
Drug: Locally Directed Therapy
Patients determined to have mutated KRAS (or KRAS not evaluable) will be assigned to an event monitoring arm in which adjuvant therapy will be determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification will be the responsibility of the treating oncologists.
|
Outcome Measures
Primary Outcome Measures
- Disease-free Survival (Arms A and D: Wild-type KRAS Patients) [At 3 years]
The primary endpoint for this study was to compare the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier.
Secondary Outcome Measures
- Disease-free Survival (Arms A and D: Mutant KRAS Patients) [At 3 years]
A secondary endpoint for this study was to investigate the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier.
- Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients) [Up to 3 years]
Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event free rates (percentage) are reported below for Wild-type KRAS Patients.
- Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients) [Up to 3 years]
Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event-free rates (percentage) are report below for mutant KRAS patients.
- Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients) [Assessed up to 8 years]
The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
- Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients) [Assessed up to 8 years]
The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Histologically confirmed adenocarcinoma of the colon
-
Stage III disease
-
No resected stage IV disease
-
No rectal cancer
-
Gross inferior (caudad) margin of the primary tumor must be ≥ 12 cm from the anal verge by rigid proctoscopy
-
Stage III tumor must have been completely resected within the past 56 days
-
Must have documented en bloc resection in patients with tumor adherence to adjacent structures
-
Tumor-related obstructions and colonic perforation are allowed
-
Tumor samples must be available
-
At least 1 pathologically confirmed positive lymph node
-
No evidence of residual involved lymph node disease
-
Synchronous primary colon cancer allowed
-
No distant metastatic disease
-
Performance status - Eastern Cooperative Oncology Group (ECOG) 0-2
-
Absolute neutrophil count ≥ 1,500/mm^3
-
Platelet count ≥ 100,000/mm^3
-
Hemoglobin ≥ 9 g/dL
-
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
-
Creatinine ≤ 1.5 times ULN
-
No uncontrolled high blood pressure
-
No unstable angina
-
No symptomatic congestive heart failure
-
No myocardial infarction with the past 6 months
-
No New York Heart Association class III or IV heart disease
-
No symptomatic pulmonary fibrosis
-
No symptomatic interstitial pneumonitis
-
No prior allergic reaction (known sensitivity) to chimerized or murine monoclonal antibody therapy
-
No known allergy to platinum compounds
-
No documented presence of human anti-mouse antibodies (HAMA)
-
No active uncontrolled bacterial, viral, or systemic fungal infection
-
HIV negative
-
No clinically defined AIDS
-
Not pregnant or nursing
-
Negative pregnancy test
-
No men or women of childbearing potential who are unwilling to employ adequate contraception
-
No inadequately treated gastrointestinal bleeding
-
No ≥ grade 2 pre-existing peripheral sensory or motor neuropathy
-
No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or lobular carcinoma in situ in 1 breast
-
No other concurrent medical condition that would preclude study participation
-
No concurrent biologic therapy
-
No prior chemotherapy for colon cancer
-
No other concurrent chemotherapy
-
No prior radiotherapy for colon cancer
-
No concurrent targeted agents
-
No prior agents directed against epidermal growth factor-receptor
-
No other concurrent anticancer therapy
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Northeast Alabama Regional Medical Center | Anniston | Alabama | United States | 36202 |
| 2 | Clearview Cancer Institute | Huntsville | Alabama | United States | 35805 |
| 3 | Mobile Infirmary Medical Center | Mobile | Alabama | United States | 36607 |
| 4 | Providence Hospital | Mobile | Alabama | United States | 36608 |
| 5 | Providence Alaska Medical Center | Anchorage | Alaska | United States | 99508 |
| 6 | Banner Thunderbird Medical Center | Glendale | Arizona | United States | 85306 |
| 7 | Banner Desert Medical Center | Mesa | Arizona | United States | 85202 |
| 8 | Banner Baywood Medical Center | Mesa | Arizona | United States | 85206 |
| 9 | Banner Good Samaritan Medical Center | Phoenix | Arizona | United States | 85006 |
| 10 | Western Regional CCOP | Phoenix | Arizona | United States | 85006 |
| 11 | Phoenix Indian Medical Center | Phoenix | Arizona | United States | 85016 |
| 12 | Scottsdale Healthcare | Scottsdale | Arizona | United States | 85251 |
| 13 | Mayo Clinic in Arizona | Scottsdale | Arizona | United States | 85259 |
| 14 | Highlands Oncology Group-Bentonville | Bentonville | Arkansas | United States | 72712 |
| 15 | Saint Edward Mercy Medical Center | Fort Smith | Arkansas | United States | 72903 |
| 16 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 17 | Veteran's Administration Medical Center | Little Rock | Arkansas | United States | 72205 |
| 18 | Alta Bates Medical Center-Herrick Campus | Berkeley | California | United States | 94704 |
| 19 | Providence Saint Joseph Medical Center | Burbank | California | United States | 91505 |
| 20 | Mills - Peninsula Hospitals | Burlingame | California | United States | 94010 |
| 21 | East Bay Radiation Oncology Center | Castro Valley | California | United States | 94546 |
| 22 | Eden Hospital Medical Center | Castro Valley | California | United States | 94546 |
| 23 | Valley Medical Oncology Consultants-Castro Valley | Castro Valley | California | United States | 94546 |
| 24 | City of Hope | Duarte | California | United States | 91010 |
| 25 | Northbay Cancer Center | Fairfield | California | United States | 94533 |
| 26 | Kaiser Permanente, Fremont | Fremont | California | United States | 94538 |
| 27 | Valley Medical Oncology Consultants-Fremont | Fremont | California | United States | 94538 |
| 28 | California Cancer Center - North Fresno | Fresno | California | United States | 93720 |
| 29 | Cancer Care Associates | Fresno | California | United States | 93720 |
| 30 | California Cancer Care - Greenbrae | Greenbrae | California | United States | 94904 |
| 31 | Sutter Health Western Division Cancer Research Group | Greenbrae | California | United States | 94904 |
| 32 | Kaiser Permanente, Hayward | Hayward | California | United States | 94545 |
| 33 | Saint Rose Hospital | Hayward | California | United States | 94545 |
| 34 | Loma Linda University Medical Center | Loma Linda | California | United States | 92354 |
| 35 | University of Southern California | Los Angeles | California | United States | 90033-0804 |
| 36 | Contra Costa Regional Medical Center | Martinez | California | United States | 94553-3156 |
| 37 | Fremont - Rideout Cancer Center | Marysville | California | United States | 95901 |
| 38 | Memorial Medical Center | Modesto | California | United States | 95355 |
| 39 | Community Hospital of Monterey Peninsula | Monterey | California | United States | 93940 |
| 40 | El Camino Hospital | Mountain View | California | United States | 94040 |
| 41 | Palo Alto Medical Foundation-Camino Division | Mountain View | California | United States | 94040 |
| 42 | Highland General Hospital | Oakland | California | United States | 94602 |
| 43 | Alta Bates Summit Medical Center - Summit Campus | Oakland | California | United States | 94609 |
| 44 | Bay Area Breast Surgeons Inc | Oakland | California | United States | 94609 |
| 45 | Bay Area Tumor Institution CCOP | Oakland | California | United States | 94609 |
| 46 | Larry G Strieff MD Medical Corporation | Oakland | California | United States | 94609 |
| 47 | Tom K Lee Inc | Oakland | California | United States | 94609 |
| 48 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 49 | Saint Joseph Hospital | Orange | California | United States | 92868 |
| 50 | Desert Regional Medical Center | Palm Springs | California | United States | 92262 |
| 51 | Palo Alto Medical Foundation Heath Care | Palo Alto | California | United States | 94301 |
| 52 | Valley Care Health System - Pleasanton | Pleasanton | California | United States | 94588 |
| 53 | Valley Medical Oncology Consultants | Pleasanton | California | United States | 94588 |
| 54 | Shasta Regional Medical Center | Redding | California | United States | 96001 |
| 55 | Kaiser Permanente-Redwood City | Redwood City | California | United States | 94063 |
| 56 | Kaiser Permanente-Richmond | Richmond | California | United States | 94801 |
| 57 | Kaiser Permanente-Roseville | Roseville | California | United States | 95661 |
| 58 | Sutter Roseville Medical Center | Roseville | California | United States | 95661 |
| 59 | Sutter General Hospital | Sacramento | California | United States | 95816 |
| 60 | UC Davis Comprehensive Cancer Center | Sacramento | California | United States | 95817 |
| 61 | Kaiser Permanente-South Sacramento | Sacramento | California | United States | 95823 |
| 62 | Kaiser Permanente - Sacramento | Sacramento | California | United States | 95825 |
| 63 | Kaiser Permanente | San Diego | California | United States | 92120 |
| 64 | Naval Medical Center -San Diego | San Diego | California | United States | 92134 |
| 65 | University of California San Diego - Veterans Administration | San Diego | California | United States | 92161 |
| 66 | Kaiser Permanente-San Francisco | San Francisco | California | United States | 94115 |
| 67 | University of California San Francisco Medical Center-Mount Zion | San Francisco | California | United States | 94115 |
| 68 | California Pacific Medical Center | San Francisco | California | United States | 94118 |
| 69 | Kaiser Permanente-Santa Teresa-San Jose | San Jose | California | United States | 95119 |
| 70 | Doctors Medical Center- JC Robinson Regional Cancer Center | San Pablo | California | United States | 94806 |
| 71 | Kaiser Permanente-San Rafael | San Rafael | California | United States | 94903 |
| 72 | Kaiser Permanente Medical Center - Santa Clara | Santa Clara | California | United States | 95051 |
| 73 | Kaiser Permanente-Santa Rosa | Santa Rosa | California | United States | 95403 |
| 74 | Santa Rosa Memorial Hospital | Santa Rosa | California | United States | 95405 |
| 75 | Kaiser Permanente-South San Francisco | South San Francisco | California | United States | 94080 |
| 76 | Kaiser Permanente-Stockton | Stockton | California | United States | 95210 |
| 77 | Tahoe Forest Cancer Center | Truckee | California | United States | 96161 |
| 78 | Kaiser Permanente-Vallejo | Vallejo | California | United States | 94589 |
| 79 | Sutter Solano Medical Center | Vallejo | California | United States | 94589 |
| 80 | Kaiser Permanente-Walnut Creek | Walnut Creek | California | United States | 94596 |
| 81 | The Medical Center of Aurora | Aurora | Colorado | United States | 80012 |
| 82 | Boulder Community Hospital | Boulder | Colorado | United States | 80301 |
| 83 | Penrose-Saint Francis Healthcare | Colorado Springs | Colorado | United States | 80907 |
| 84 | Memorial Hospital Colorado Springs | Colorado Springs | Colorado | United States | 80909 |
| 85 | Saint Anthony Central Hospital | Denver | Colorado | United States | 80204 |
| 86 | Porter Adventist Hospital | Denver | Colorado | United States | 80210 |
| 87 | Exempla Saint Joseph Hospital | Denver | Colorado | United States | 80218 |
| 88 | Presbyterian - Saint Lukes Medical Center - Health One | Denver | Colorado | United States | 80218 |
| 89 | Rose Medical Center | Denver | Colorado | United States | 80220 |
| 90 | Colorado Cancer Research Program CCOP | Denver | Colorado | United States | 80224-2522 |
| 91 | Swedish Medical Center | Englewood | Colorado | United States | 80110 |
| 92 | Poudre Valley Hospital | Fort Collins | Colorado | United States | 80524 |
| 93 | Front Range Cancer Specialists | Fort Collins | Colorado | United States | 80528 |
| 94 | Saint Mary's Hospital and Regional Medical Center | Grand Junction | Colorado | United States | 81502 |
| 95 | North Colorado Medical Center | Greeley | Colorado | United States | 80631 |
| 96 | Sky Ridge Medical Center | Lone Tree | Colorado | United States | 80124 |
| 97 | Longmont United Hospital | Longmont | Colorado | United States | 80501 |
| 98 | McKee Medical Center | Loveland | Colorado | United States | 80539 |
| 99 | Saint Mary Corwin Medical Center | Pueblo | Colorado | United States | 81004 |
| 100 | North Suburban Medical Center | Thornton | Colorado | United States | 80229 |
| 101 | Exempla Lutheran Medical Center | Wheat Ridge | Colorado | United States | 80033 |
| 102 | Bridgeport Hospital | Bridgeport | Connecticut | United States | 06610 |
| 103 | Danbury Hospital | Danbury | Connecticut | United States | 06810 |
| 104 | Hartford Hospital | Hartford | Connecticut | United States | 06102 |
| 105 | Saint Francis Hospital and Medical Center | Hartford | Connecticut | United States | 06105 |
| 106 | Manchester Memorial Hospital | Manchester | Connecticut | United States | 06040 |
| 107 | Middlesex Hospital | Middletown | Connecticut | United States | 06457 |
| 108 | The Hospital of Central Connecticut | New Britain | Connecticut | United States | 06050 |
| 109 | Eastern Connecticut Hematology and Oncology Associates | Norwich | Connecticut | United States | 06360 |
| 110 | Stamford Hospital | Stamford | Connecticut | United States | 06904 |
| 111 | Bayhealth Medical Center at Kent General | Dover | Delaware | United States | 19901 |
| 112 | Beebe Medical Center | Lewes | Delaware | United States | 19958 |
| 113 | Washington Hospital Center | Washington | District of Columbia | United States | 20010 |
| 114 | Lombardi Comprehensive Cancer Center at Georgetown University | Washington | District of Columbia | United States | 20057 |
| 115 | Howard University Hospital | Washington | District of Columbia | United States | 20060 |
| 116 | Halifax Medical Center-Centers for Oncology | Daytona Beach | Florida | United States | 32114 |
| 117 | North Broward Medical Center | Deerfield Beach | Florida | United States | 33064 |
| 118 | Broward General Medical Center | Fort Lauderdale | Florida | United States | 33316 |
| 119 | University of Florida | Gainesville | Florida | United States | 32610 |
| 120 | Edna Williams Cancer Center at the Baptist Cancer Institute | Jacksonville | Florida | United States | 32207 |
| 121 | Mayo Clinic in Florida | Jacksonville | Florida | United States | 32224-9980 |
| 122 | The Watson Clinic | Lakeland | Florida | United States | 33805 |
| 123 | Cancer Centers of Central Florida PA | Leesburg | Florida | United States | 34788 |
| 124 | Baptist Hospital of Miami | Miami | Florida | United States | 33176 |
| 125 | Integrated Community Oncology Network - Orange Park Cancer Center | Orange Park | Florida | United States | 32073 |
| 126 | Florida Hospital | Orlando | Florida | United States | 32803 |
| 127 | M D Anderson Cancer Center- Orlando | Orlando | Florida | United States | 32806 |
| 128 | Sacred Heart Hospital | Pensacola | Florida | United States | 32504 |
| 129 | Sacred Heart Medical Oncology Group - Davis Highway | Pensacola | Florida | United States | 32514 |
| 130 | Montgomery and Associates MD PA | Saint Augustine | Florida | United States | 32086 |
| 131 | Florida Cancer Specialists - Sarasota Downtown | Sarasota | Florida | United States | 34236 |
| 132 | Martin Memorial Cancer Center | Stuart | Florida | United States | 34994 |
| 133 | Martin Memorial Medical Center - North | Stuart | Florida | United States | 34994 |
| 134 | Martin Memorial Hospital - South | Stuart | Florida | United States | 34997 |
| 135 | Palm Beach Cancer Institute-Main Office | West Palm Beach | Florida | United States | 33401 |
| 136 | Phoebe Putney Memorial Hospital | Albany | Georgia | United States | 31703 |
| 137 | Piedmont Hospital | Atlanta | Georgia | United States | 30309 |
| 138 | Atlanta Regional CCOP | Atlanta | Georgia | United States | 30342 |
| 139 | Northside Hospital | Atlanta | Georgia | United States | 30342 |
| 140 | Saint Joseph's Hospital of Atlanta | Atlanta | Georgia | United States | 30342 |
| 141 | Augusta Oncology Associates PC | Augusta | Georgia | United States | 30901 |
| 142 | Well Star Cobb Hospital | Austell | Georgia | United States | 30106 |
| 143 | John B Amos Cancer Center | Columbus | Georgia | United States | 31904 |
| 144 | Dekalb Medical Center | Decatur | Georgia | United States | 30033 |
| 145 | Veterans Administration Medical Center | Decatur | Georgia | United States | 30033 |
| 146 | Northeast Georgia Medical Center | Gainesville | Georgia | United States | 30501 |
| 147 | Gwinnett Medical Center | Lawrenceville | Georgia | United States | 30045 |
| 148 | Wellstar Kennestone Hospital | Marietta | Georgia | United States | 30060 |
| 149 | Southern Regional Medical Center | Riverdale | Georgia | United States | 30274 |
| 150 | Memorial Health University Medical Center | Savannah | Georgia | United States | 31403 |
| 151 | Saint Joseph's-Candler Health System | Savannah | Georgia | United States | 31405 |
| 152 | South Georgia Medical Center | Valdosta | Georgia | United States | 31603 |
| 153 | Kapiolani Medical Center at Pali Momi | 'Aiea | Hawaii | United States | 96701 |
| 154 | Oncare Hawaii Inc-POB II | Honolulu | Hawaii | United States | 96813 |
| 155 | Queen's Medical Center | Honolulu | Hawaii | United States | 96813 |
| 156 | Straub Clinic and Hospital | Honolulu | Hawaii | United States | 96813 |
| 157 | University of Hawaii | Honolulu | Hawaii | United States | 96813 |
| 158 | Hawaii Medical Center East | Honolulu | Hawaii | United States | 96817 |
| 159 | Oncare Hawaii Inc-Kuakini | Honolulu | Hawaii | United States | 96817 |
| 160 | Kapiolani Medical Center for Women and Children | Honolulu | Hawaii | United States | 96826 |
| 161 | Tripler Army Medical Center | Honolulu | Hawaii | United States | 96859 |
| 162 | Maui Memorial Medical Center | Wailuku | Hawaii | United States | 96793 |
| 163 | Pacific Cancer Institute of Maui | Wailuku | Hawaii | United States | 96793 |
| 164 | Saint Alphonsus Regional Medical Center | Boise | Idaho | United States | 83706 |
| 165 | Saint Luke's Mountain States Tumor Institute | Boise | Idaho | United States | 83712 |
| 166 | Saint Anthony's Health | Alton | Illinois | United States | 62002 |
| 167 | Rush - Copley Medical Center | Aurora | Illinois | United States | 60504 |
| 168 | Saint Joseph Medical Center | Bloomington | Illinois | United States | 61701 |
| 169 | Graham Hospital Association | Canton | Illinois | United States | 61520 |
| 170 | Memorial Hospital | Carthage | Illinois | United States | 62321 |
| 171 | Mount Sinai Hospital Medical Center | Chicago | Illinois | United States | 60608 |
| 172 | Hematology and Oncology Associates | Chicago | Illinois | United States | 60611 |
| 173 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 174 | John H Stroger Jr Hospital of Cook County | Chicago | Illinois | United States | 60612-3785 |
| 175 | Mercy Hospital and Medical Center | Chicago | Illinois | United States | 60616 |
| 176 | Swedish Covenant Hospital | Chicago | Illinois | United States | 60625 |
| 177 | Resurrection Healthcare | Chicago | Illinois | United States | 60631 |
| 178 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637-1470 |
| 179 | Weiss Memorial Hospital | Chicago | Illinois | United States | 60640 |
| 180 | Illinois Masonic Medical Center | Chicago | Illinois | United States | 60657 |
| 181 | Decatur Memorial Hospital | Decatur | Illinois | United States | 62526 |
| 182 | Saint Anthony Memorial Hospital | Effingham | Illinois | United States | 62401 |
| 183 | Sherman Hospital | Elgin | Illinois | United States | 60123 |
| 184 | Cancer Institute at Alexian Brothers | Elk Grove Village | Illinois | United States | 60007 |
| 185 | Eureka Hospital | Eureka | Illinois | United States | 61530 |
| 186 | Evanston CCOP-NorthShore University HealthSystem | Evanston | Illinois | United States | 60201 |
| 187 | Saint Francis Hospital | Evanston | Illinois | United States | 60202 |
| 188 | Galesburg Clinic | Galesburg | Illinois | United States | 61401 |
| 189 | Galesburg Cottage Hospital | Galesburg | Illinois | United States | 61401 |
| 190 | Intercommunity Cancer Center | Galesburg | Illinois | United States | 61401 |
| 191 | Ingalls Memorial Hospital | Harvey | Illinois | United States | 60426 |
| 192 | Mason District Hospital | Havana | Illinois | United States | 62644 |
| 193 | Hopedale Medical Complex - Hospital | Hopedale | Illinois | United States | 61747 |
| 194 | Midwest Center for Hematology Oncology | Joliet | Illinois | United States | 60432 |
| 195 | Joliet Oncology-Hematology Associates Limited | Joliet | Illinois | United States | 60435 |
| 196 | Provena Saint Mary's Hospital | Kankakee | Illinois | United States | 60901 |
| 197 | Kewanee Hospital | Kewanee | Illinois | United States | 61443 |
| 198 | La Grange Memorial Hospital | La Grange | Illinois | United States | 60525 |
| 199 | Deerpath Medical Associates | Lake Forest | Illinois | United States | 60045 |
| 200 | North Shore Hematology Oncology | Libertyville | Illinois | United States | 60048 |
| 201 | Mcdonough District Hospital | Macomb | Illinois | United States | 61455 |
| 202 | Loyola University Medical Center | Maywood | Illinois | United States | 60153 |
| 203 | Garneau, Stewart C MD (UIA Investigator) | Moline | Illinois | United States | 61265 |
| 204 | Porubcin, Michael MD (UIA Investigator) | Moline | Illinois | United States | 61265 |
| 205 | Sharis, Christine M MD (UIA Investigator) | Moline | Illinois | United States | 61265 |
| 206 | Stoffel, Thomas J MD (UIA Investigator) | Moline | Illinois | United States | 61265 |
| 207 | Trinity Medical Center | Moline | Illinois | United States | 61265 |
| 208 | Vigliotti, Antonio, P.G. M.D. (UIA Investigator) | Moline | Illinois | United States | 61265 |
| 209 | Good Samaritan Regional Medical Center | Mount Vernon | Illinois | United States | 62864 |
| 210 | Hematology Oncology Consultants Limited | Naperville | Illinois | United States | 60540 |
| 211 | Edward Hospital | Naperville | Illinois | United States | 60566 |
| 212 | Cancer Care and Hematology Specialists of Chicagoland PC | Niles | Illinois | United States | 60714 |
| 213 | Bromenn Regional Medical Center | Normal | Illinois | United States | 61761 |
| 214 | Community Cancer Center Foundation | Normal | Illinois | United States | 61761 |
| 215 | Advocate Christ Medical Center | Oak Lawn | Illinois | United States | 60453-2699 |
| 216 | Illinois CancerCare-Ottawa Clinic | Ottawa | Illinois | United States | 61350 |
| 217 | Ottawa Regional Hospital and Healthcare Center | Ottawa | Illinois | United States | 61350 |
| 218 | Pekin Cancer Treatment Center | Pekin | Illinois | United States | 61554 |
| 219 | Pekin Hospital | Pekin | Illinois | United States | 61554 |
| 220 | Methodist Medical Center of Illinois | Peoria | Illinois | United States | 61603 |
| 221 | Proctor Hospital | Peoria | Illinois | United States | 61614 |
| 222 | Illinois CancerCare-Peoria | Peoria | Illinois | United States | 61615 |
| 223 | Illinois Oncology Research Association CCOP | Peoria | Illinois | United States | 61615 |
| 224 | OSF Saint Francis Medical Center | Peoria | Illinois | United States | 61637 |
| 225 | Illinois Valley Hospital | Peru | Illinois | United States | 61354 |
| 226 | Perry Memorial Hospital | Princeton | Illinois | United States | 61356 |
| 227 | West Suburban Cancer Center | River Forest | Illinois | United States | 60305 |
| 228 | Swedish American Hospital | Rockford | Illinois | United States | 61104 |
| 229 | Sarah Culbertson Memorial Hospital | Rushville | Illinois | United States | 62681 |
| 230 | Edward H Kaplan MD and Associates | Skokie | Illinois | United States | 60076 |
| 231 | Hematology Oncology Associates of Illinois - Skokie | Skokie | Illinois | United States | 60076 |
| 232 | Midwest Cancer Research Group Incorporated | Skokie | Illinois | United States | 60077 |
| 233 | Saint Margaret's Hospital | Spring Valley | Illinois | United States | 61362 |
| 234 | Valley Cancer Center | Spring Valley | Illinois | United States | 61362 |
| 235 | Memorial Medical Center | Springfield | Illinois | United States | 62781-0001 |
| 236 | Carle Clinic-Urbana Main | Urbana | Illinois | United States | 61801 |
| 237 | Carle Foundation dba Carle Cancer Center | Urbana | Illinois | United States | 61801 |
| 238 | Saint Francis Hospital and Health Centers | Beech Grove | Indiana | United States | 46107 |
| 239 | Elkhart General Hospital | Elkhart | Indiana | United States | 46515 |
| 240 | Fort Wayne Medical Oncology and Hematology Inc - State Boulevard | Fort Wayne | Indiana | United States | 46845 |
| 241 | Indiana University Medical Center | Indianapolis | Indiana | United States | 46202 |
| 242 | Richard L. Roudebush Veterans Affairs Medical Center | Indianapolis | Indiana | United States | 46202 |
| 243 | Wishard Hospital | Indianapolis | Indiana | United States | 46202 |
| 244 | Saint Vincent Hospital and Health Services | Indianapolis | Indiana | United States | 46260 |
| 245 | Howard Regional Healthcare System | Kokomo | Indiana | United States | 46904 |
| 246 | Laporte Hospital | La Porte | Indiana | United States | 46350 |
| 247 | Clarian Arnett Cancer Care | Lafayette | Indiana | United States | 47904 |
| 248 | Premier Oncology Hematology Associates | Merrillville | Indiana | United States | 46410 |
| 249 | Saint Anthony Memorial Health Center | Michigan City | Indiana | United States | 46360 |
| 250 | Ball Memorial Hospital | Muncie | Indiana | United States | 47303 |
| 251 | The Community Hospital | Munster | Indiana | United States | 46321 |
| 252 | Reid Hospital and Health Care Services | Richmond | Indiana | United States | 47374 |
| 253 | Memorial Hospital of South Bend | South Bend | Indiana | United States | 46601 |
| 254 | Northern Indiana Cancer Research Consortium | South Bend | Indiana | United States | 46601 |
| 255 | Saint Joseph's Medical Center | South Bend | Indiana | United States | 46617 |
| 256 | South Bend Clinic | South Bend | Indiana | United States | 46617 |
| 257 | McFarland Clinic | Ames | Iowa | United States | 50010 |
| 258 | Constantinou, Costas L MD (UIA Investigator) | Bettendorf | Iowa | United States | 52722 |
| 259 | Hematology Oncology Associates-Quad Cities | Bettendorf | Iowa | United States | 52722 |
| 260 | Saint Anthony Regional Hospital | Carroll | Iowa | United States | 51401 |
| 261 | Iowa Blood and Cancer Care PLC | Cedar Rapids | Iowa | United States | 52402 |
| 262 | Saint Luke's Hospital | Cedar Rapids | Iowa | United States | 52402 |
| 263 | Cedar Rapids Oncology Association | Cedar Rapids | Iowa | United States | 52403 |
| 264 | Mercy Hospital | Cedar Rapids | Iowa | United States | 52403 |
| 265 | Oncology Associates | Cedar Rapids | Iowa | United States | 52403 |
| 266 | Medical Oncology and Hematology Associates-West Des Moines | Clive | Iowa | United States | 50325 |
| 267 | Alegent Health Mercy Hospital | Council Bluffs | Iowa | United States | 51503 |
| 268 | Genesis Medical Center - East Campus | Davenport | Iowa | United States | 52803 |
| 269 | Genesis Medical Center - West Campus | Davenport | Iowa | United States | 52804 |
| 270 | Mercy Capitol | Des Moines | Iowa | United States | 50307 |
| 271 | Iowa Methodist Medical Center | Des Moines | Iowa | United States | 50309 |
| 272 | Iowa Oncology Research Association CCOP | Des Moines | Iowa | United States | 50309 |
| 273 | Medical Oncology and Hematology Associates-Des Moines | Des Moines | Iowa | United States | 50309 |
| 274 | Medical Oncology and Hematology Associates | Des Moines | Iowa | United States | 50314 |
| 275 | Mercy Medical Center - Des Moines | Des Moines | Iowa | United States | 50314 |
| 276 | Iowa Lutheran Hospital | Des Moines | Iowa | United States | 50316 |
| 277 | Finley Hospital | Dubuque | Iowa | United States | 52001 |
| 278 | University of Iowa Hospitals and Clinics | Iowa City | Iowa | United States | 52242 |
| 279 | Mercy Medical Center - North Iowa | Mason City | Iowa | United States | 50401 |
| 280 | Community Memorial Hospital | Missouri Valley | Iowa | United States | 51555 |
| 281 | Burgess Memorial Hospital | Onawa | Iowa | United States | 51040 |
| 282 | Siouxland Regional Cancer Center | Sioux City | Iowa | United States | 51101-1733 |
| 283 | Siouxland Hematology - Oncology Associates | Sioux City | Iowa | United States | 51101 |
| 284 | Mercy Medical Center-Sioux City | Sioux City | Iowa | United States | 51104 |
| 285 | Saint Luke's Regional Medical Center | Sioux City | Iowa | United States | 51104 |
| 286 | Covenant Medical Center | Waterloo | Iowa | United States | 50702 |
| 287 | Memorial Hospital of Arkansas City | Arkansas City | Kansas | United States | 67005 |
| 288 | Cancer Center of Kansas - Chanute | Chanute | Kansas | United States | 66720 |
| 289 | Cancer Center of Kansas - Dodge City | Dodge City | Kansas | United States | 67801 |
| 290 | Cancer Center of Kansas - El Dorado | El Dorado | Kansas | United States | 67042 |
| 291 | Cancer Center of Kansas-Independence | Independence | Kansas | United States | 67301 |
| 292 | Providence Medical Center | Kansas City | Kansas | United States | 66112 |
| 293 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 294 | Cancer Center of Kansas-Kingman | Kingman | Kansas | United States | 67068 |
| 295 | Lawrence Memorial Hospital | Lawrence | Kansas | United States | 66044 |
| 296 | Cancer Center of Kansas - McPherson | McPherson | Kansas | United States | 67460 |
| 297 | Cancer Center of Kansas - Newton | Newton | Kansas | United States | 67114 |
| 298 | Olathe Medical Center | Olathe | Kansas | United States | 66061 |
| 299 | Cancer Center of Kansas - Ottawa | Ottawa | Kansas | United States | 66067 |
| 300 | Menorah Medical Center | Overland Park | Kansas | United States | 66209 |
| 301 | Radiation Oncology Practice Corporation Southwest | Overland Park | Kansas | United States | 66210 |
| 302 | Cancer Center of Kansas - Parsons | Parsons | Kansas | United States | 67357 |
| 303 | Mount Carmel Regional Cancer Center | Pittsburg | Kansas | United States | 66762 |
| 304 | Cancer Center of Kansas - Pratt | Pratt | Kansas | United States | 67124 |
| 305 | Cancer Center of Kansas - Salina | Salina | Kansas | United States | 67401 |
| 306 | Shawnee Mission Medical Center | Shawnee Mission | Kansas | United States | 66204 |
| 307 | Stormont-Vail Regional Health Center | Topeka | Kansas | United States | 66604 |
| 308 | Saint Francis Hospital and Medical Center - Topeka | Topeka | Kansas | United States | 66606 |
| 309 | Cancer Center of Kansas - Wellington | Wellington | Kansas | United States | 67152 |
| 310 | Associates In Womens Health | Wichita | Kansas | United States | 67208 |
| 311 | Cancer Center of Kansas-Wichita Medical Arts Tower | Wichita | Kansas | United States | 67208 |
| 312 | Cancer Center of Kansas - Main Office | Wichita | Kansas | United States | 67214 |
| 313 | Via Christi Regional Medical Center | Wichita | Kansas | United States | 67214 |
| 314 | Wichita CCOP | Wichita | Kansas | United States | 67214 |
| 315 | Cancer Center of Kansas - Winfield | Winfield | Kansas | United States | 67156 |
| 316 | Our Lady Bellefonte Hospital | Ashland | Kentucky | United States | 41101 |
| 317 | Central Baptist Hospital | Lexington | Kentucky | United States | 40503 |
| 318 | University of Louisville | Louisville | Kentucky | United States | 40292 |
| 319 | Merle Mahr Cancer Center | Madisonville | Kentucky | United States | 42431 |
| 320 | Baton Rouge General Medical Center | Baton Rouge | Louisiana | United States | 70806 |
| 321 | Mary Bird Perkins Cancer Center | Baton Rouge | Louisiana | United States | 70809 |
| 322 | Ochsner Clinic Foundation-Baton Rouge | Baton Rouge | Louisiana | United States | 70809 |
| 323 | DeSoto Regional Health System | Mansfield | Louisiana | United States | 71052 |
| 324 | Metairie Oncologists | Metairie | Louisiana | United States | 70006 |
| 325 | Louisiana State University Sciences Center- Monroe | Monroe | Louisiana | United States | 71210 |
| 326 | Louisiana State University Health Science Center | New Orleans | Louisiana | United States | 70112 |
| 327 | Medical Center of Louisiana | New Orleans | Louisiana | United States | 70112 |
| 328 | Ochsner Clinic CCOP | New Orleans | Louisiana | United States | 70121 |
| 329 | Ochsner Clinic Foundation | New Orleans | Louisiana | United States | 70121 |
| 330 | Highland Clinic | Shreveport | Louisiana | United States | 71105 |
| 331 | Louisiana State University | Shreveport | Louisiana | United States | 71130 |
| 332 | Eastern Maine Medical Center | Bangor | Maine | United States | 04401 |
| 333 | Anne Arundel Medical Center | Annapolis | Maryland | United States | 21401 |
| 334 | Greater Baltimore Medical Center | Baltimore | Maryland | United States | 21204 |
| 335 | The Union Memorial Hospital | Baltimore | Maryland | United States | 21218 |
| 336 | Franklin Square Hospital Center | Baltimore | Maryland | United States | 21237 |
| 337 | Good Samaritan Hospital of Maryland | Baltimore | Maryland | United States | 21239 |
| 338 | Johns Hopkins University | Baltimore | Maryland | United States | 21287-8936 |
| 339 | Union Hospital of Cecil County | Elkton | Maryland | United States | 21921 |
| 340 | Frederick Memorial Hospital | Frederick | Maryland | United States | 21701 |
| 341 | Washington County Hospital | Hagerstown | Maryland | United States | 21740 |
| 342 | Associates in Oncology Hematology PC -Kensington | Kensington | Maryland | United States | 20895 |
| 343 | Associates In Oncology Hematology PC-Rockville | Rockville | Maryland | United States | 20878 |
| 344 | Beverly Hospital | Beverly | Massachusetts | United States | 01915 |
| 345 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 346 | Brigham and Women's Hospital | Boston | Massachusetts | United States | 02115 |
| 347 | Dana-Farber Cancer Institute | Boston | Massachusetts | United States | 02115 |
| 348 | Boston Medical Center | Boston | Massachusetts | United States | 02118 |
| 349 | Beth Israel Deaconess Medical Center | Boston | Massachusetts | United States | 02215 |
| 350 | Caritas Saint Elizabeth's Medical Center | Brighton | Massachusetts | United States | 02135-2997 |
| 351 | Addison Gilbert Hospital | Gloucester | Massachusetts | United States | 01930 |
| 352 | Franklin Medical Center | Greenfield | Massachusetts | United States | 01301 |
| 353 | Holyoke Medical Center | Holyoke | Massachusetts | United States | 01040 |
| 354 | Lowell General Hospital | Lowell | Massachusetts | United States | 01854 |
| 355 | Lawrence Memorial | Medford | Massachusetts | United States | 02155 |
| 356 | Holy Family Hospital | Methuen | Massachusetts | United States | 01844 |
| 357 | Metrowest Medical Center Incorporated | Natick | Massachusetts | United States | 01760 |
| 358 | Norwood Hospital | Norwood | Massachusetts | United States | 02062 |
| 359 | North Shore Medical Center Cancer Center | Peabody | Massachusetts | United States | 01960 |
| 360 | Berkshire Hematology Oncology PC | Pittsfield | Massachusetts | United States | 01201 |
| 361 | Commonwealth Hematology Oncology PC-Quincy | Quincy | Massachusetts | United States | 02169 |
| 362 | South Shore Hospital | South Weymouth | Massachusetts | United States | 02190 |
| 363 | Baystate Medical Center | Springfield | Massachusetts | United States | 01199 |
| 364 | Morton Hospital and Medical Center | Taunton | Massachusetts | United States | 02780 |
| 365 | Noble Hospital | Westfield | Massachusetts | United States | 01085 |
| 366 | Bixby Medical Center | Adrian | Michigan | United States | 49221 |
| 367 | Hickman Cancer Center | Adrian | Michigan | United States | 49221 |
| 368 | Saint Joseph Mercy Hospital | Ann Arbor | Michigan | United States | 48106-0995 |
| 369 | Michigan Cancer Research Consortium Community Clinical Oncology Program | Ann Arbor | Michigan | United States | 48106 |
| 370 | Battle Creek Health System | Battle Creek | Michigan | United States | 49017 |
| 371 | Bay Regional Medical Center | Bay City | Michigan | United States | 48708 |
| 372 | Mecosta County Medical Center | Big Rapids | Michigan | United States | 49307 |
| 373 | Oakwood Hospital | Dearborn | Michigan | United States | 48123 |
| 374 | Wayne State University | Detroit | Michigan | United States | 48202 |
| 375 | Saint John Hospital and Medical Center | Detroit | Michigan | United States | 48236 |
| 376 | Michigan State University - Breslin Cancer Center | East Lansing | Michigan | United States | 48824-1313 |
| 377 | Green Bay Oncology - Escanaba | Escanaba | Michigan | United States | 49431 |
| 378 | Hurley Medical Center | Flint | Michigan | United States | 48502 |
| 379 | Genesys Regional Medical Center | Flint | Michigan | United States | 48532 |
| 380 | McLaren Regional Medical Center | Flint | Michigan | United States | 48532 |
| 381 | Grand Rapids Clinical Oncology Program | Grand Rapids | Michigan | United States | 49503 |
| 382 | Saint Mary's Health Care | Grand Rapids | Michigan | United States | 49503 |
| 383 | Spectrum Health at Butterworth Campus | Grand Rapids | Michigan | United States | 49503 |
| 384 | Spectrum Health-Blodgett Campus | Grand Rapids | Michigan | United States | 49506 |
| 385 | Holland Community Hospital | Holland | Michigan | United States | 49423 |
| 386 | Green Bay Oncology - Iron Mountain | Iron Mountain | Michigan | United States | 49801 |
| 387 | Allegiance Health | Jackson | Michigan | United States | 49201 |
| 388 | Borgess Medical Center | Kalamazoo | Michigan | United States | 49001 |
| 389 | Bronson Methodist Hospital | Kalamazoo | Michigan | United States | 49007 |
| 390 | West Michigan Cancer Center | Kalamazoo | Michigan | United States | 49007 |
| 391 | Kalamazoo Center for Medical Studies | Kalamazoo | Michigan | United States | 49008 |
| 392 | Ingham Regional Medical Center | Lansing | Michigan | United States | 48910 |
| 393 | Sparrow Hospital | Lansing | Michigan | United States | 48912 |
| 394 | Lapeer Regional Hospital | Lapeer | Michigan | United States | 48446 |
| 395 | Saint Mary Mercy Hospital | Livonia | Michigan | United States | 48154 |
| 396 | Mid-Michigan Medical Center - Midland | Midland | Michigan | United States | 48670 |
| 397 | Community Cancer Center of Monroe | Monroe | Michigan | United States | 48162 |
| 398 | Mercy Memorial Hospital | Monroe | Michigan | United States | 48162 |
| 399 | Mercy Health Partners-Hackley Campus | Muskegon | Michigan | United States | 49442 |
| 400 | Mercy Health Partners-Mercy Campus | Muskegon | Michigan | United States | 49443 |
| 401 | Northern Michigan Regional Hospital | Petoskey | Michigan | United States | 49770 |
| 402 | Saint Joseph Mercy Oakland | Pontiac | Michigan | United States | 48341-2985 |
| 403 | Saint Joseph Mercy Port Huron | Port Huron | Michigan | United States | 48060 |
| 404 | William Beaumont Hospital | Royal Oak | Michigan | United States | 48073 |
| 405 | Saint Mary's of Michigan | Saginaw | Michigan | United States | 48601 |
| 406 | Lakeland Hospital | Saint Joseph | Michigan | United States | 49085 |
| 407 | Providence Hospital | Southfield | Michigan | United States | 48075 |
| 408 | Munson Medical Center | Traverse City | Michigan | United States | 49684 |
| 409 | Saint John Macomb-Oakland Hospital | Warren | Michigan | United States | 48093 |
| 410 | Metro Health Hospital | Wyoming | Michigan | United States | 49519 |
| 411 | Harris, John Gilbert MD (UIA Investigator) | Alexandria | Minnesota | United States | 56308 |
| 412 | Medini, Eitan MD (UIA Investigator) | Alexandria | Minnesota | United States | 56308 |
| 413 | Merit Care Clinic Bemidji | Bemidji | Minnesota | United States | 56601 |
| 414 | Brainerd Medical Center Inc | Brainerd | Minnesota | United States | 56401 |
| 415 | Saint Joseph's Medical Center | Brainerd | Minnesota | United States | 56401 |
| 416 | Fairview Ridges Hospital | Burnsville | Minnesota | United States | 55337 |
| 417 | Mercy Hospital | Coon Rapids | Minnesota | United States | 55433 |
| 418 | Duluth Clinic CCOP | Duluth | Minnesota | United States | 55805 |
| 419 | Miller-Dwan Hospital | Duluth | Minnesota | United States | 55805 |
| 420 | Saint Luke's Hospital of Duluth | Duluth | Minnesota | United States | 55805 |
| 421 | Saint Mary's Medical Center | Duluth | Minnesota | United States | 55805 |
| 422 | Fairview-Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 423 | Etzell, Paul S MD (UIA Investigator) | Fergus Falls | Minnesota | United States | 56537 |
| 424 | Swenson, Wade II, MD (UIA Investigator) | Fergus Falls | Minnesota | United States | 56537 |
| 425 | Unity Hospital | Fridley | Minnesota | United States | 55432 |
| 426 | Hutchinson Area Health Care | Hutchinson | Minnesota | United States | 55350 |
| 427 | Meeker County Memorial Hospital | Litchfield | Minnesota | United States | 55355 |
| 428 | Immanuel-Saint Joseph Hospital-Mayo Health System | Mankato | Minnesota | United States | 56002 |
| 429 | Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota | United States | 55109 |
| 430 | Saint John's Hospital - Healtheast | Maplewood | Minnesota | United States | 55109 |
| 431 | Abbott-Northwestern Hospital | Minneapolis | Minnesota | United States | 55407 |
| 432 | Virginia Piper Cancer Institute | Minneapolis | Minnesota | United States | 55407 |
| 433 | Hennepin County Medical Center | Minneapolis | Minnesota | United States | 55415 |
| 434 | Minneapolis Veterans Medical Center | Minneapolis | Minnesota | United States | 55417 |
| 435 | Chippewa County - Montevideo Hospital | Montevideo | Minnesota | United States | 56265 |
| 436 | North Memorial Medical Health Center | Robbinsdale | Minnesota | United States | 55422 |
| 437 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 438 | CentraCare Clinic | Saint Cloud | Minnesota | United States | 56303 |
| 439 | Saint Cloud Hospital | Saint Cloud | Minnesota | United States | 56303 |
| 440 | Metro-Minnesota CCOP | Saint Louis Park | Minnesota | United States | 55416 |
| 441 | Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota | United States | 55416 |
| 442 | Regions Hospital | Saint Paul | Minnesota | United States | 55101 |
| 443 | Saint Joseph's Hospital - Healtheast | Saint Paul | Minnesota | United States | 55102 |
| 444 | United Hospital | Saint Paul | Minnesota | United States | 55102 |
| 445 | Adult and Pediatric Urology PLLP | Sartell | Minnesota | United States | 56377 |
| 446 | Saint Francis Regional Medical Center | Shakopee | Minnesota | United States | 55379 |
| 447 | Ridgeview Medical Center | Waconia | Minnesota | United States | 55387 |
| 448 | Rice Memorial Hospital | Willmar | Minnesota | United States | 56201 |
| 449 | Minnesota Oncology and Hematology PA-Woodbury | Woodbury | Minnesota | United States | 55125 |
| 450 | Woodwinds Health Campus | Woodbury | Minnesota | United States | 55125 |
| 451 | Veterans Affairs Medical Center | Jackson | Mississippi | United States | 39216 |
| 452 | Keesler Medical Center | Keesler Air Force Base | Mississippi | United States | 39534 |
| 453 | Singing River Hospital | Pascagoula | Mississippi | United States | 39581 |
| 454 | Southeast Missouri Hospital | Cape Girardeau | Missouri | United States | 63701 |
| 455 | Saint Francis Medical Center | Cape Girardeau | Missouri | United States | 63703 |
| 456 | Missouri Cancer Associates | Columbia | Missouri | United States | 65201 |
| 457 | Independence Regional Health Center | Independence | Missouri | United States | 64050 |
| 458 | Freeman Health System | Joplin | Missouri | United States | 64804 |
| 459 | Saint John's Regional Medical Center | Joplin | Missouri | United States | 64804 |
| 460 | Truman Medical Center | Kansas City | Missouri | United States | 64108 |
| 461 | Saint Luke's Cancer Institute | Kansas City | Missouri | United States | 64111 |
| 462 | Saint Luke's Hospital of Kansas City | Kansas City | Missouri | United States | 64111 |
| 463 | Radiation Oncology Practice Corporation South | Kansas City | Missouri | United States | 64114 |
| 464 | Saint Joseph Health Center | Kansas City | Missouri | United States | 64114 |
| 465 | Liberty Radiation Oncology Clinic | Kansas City | Missouri | United States | 64116 |
| 466 | North Kansas City Hospital | Kansas City | Missouri | United States | 64116 |
| 467 | Kansas City Veterans Affairs Medical Center | Kansas City | Missouri | United States | 64128 |
| 468 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
| 469 | Radiation Oncology Practice Corporation - North | Kansas City | Missouri | United States | 64154 |
| 470 | Liberty Hospital | Liberty | Missouri | United States | 64068 |
| 471 | Missouri Cancer Care PC - Saint Charles | Saint Charles | Missouri | United States | 63301 |
| 472 | Heartland Regional Medical Center | Saint Joseph | Missouri | United States | 64506 |
| 473 | Saint Louis Cancer and Breast Institute | Saint Louis | Missouri | United States | 63109 |
| 474 | Saint Louis University Hospital | Saint Louis | Missouri | United States | 63110 |
| 475 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 476 | Saint Anthony's Medical Center | Saint Louis | Missouri | United States | 63128 |
| 477 | Missouri Baptist Medical Center | Saint Louis | Missouri | United States | 63131 |
| 478 | Christian Hospital Northeast - Northwest | Saint Louis | Missouri | United States | 63136 |
| 479 | Center for Cancer Care and Research | Saint Louis | Missouri | United States | 63141 |
| 480 | Saint John's Mercy Medical Center | Saint Louis | Missouri | United States | 63141 |
| 481 | Saint Louis-Cape Girardeau CCOP | Saint Louis | Missouri | United States | 63141 |
| 482 | Ozark Health Ventures LLC dba Cancer Research for The Ozarks Springfield | Springfield | Missouri | United States | 65802 |
| 483 | Saint John's Hospital | Springfield | Missouri | United States | 65804 |
| 484 | Cox Medical Center | Springfield | Missouri | United States | 65807 |
| 485 | Hematology-Oncology Centers of the Northern Rockies PC | Billings | Montana | United States | 59101 |
| 486 | Montana Cancer Consortium CCOP | Billings | Montana | United States | 59101 |
| 487 | Northern Rockies Radiation Oncology Center | Billings | Montana | United States | 59101 |
| 488 | Saint Vincent Healthcare | Billings | Montana | United States | 59101 |
| 489 | Billings Clinic | Billings | Montana | United States | 59107-7000 |
| 490 | Deaconess Medical Center | Billings | Montana | United States | 59107 |
| 491 | Bozeman Deaconess Cancer Center | Bozeman | Montana | United States | 59715 |
| 492 | Bozeman Deaconess Hospital | Bozeman | Montana | United States | 59715 |
| 493 | Internal Medicine of Bozeman | Bozeman | Montana | United States | 59715 |
| 494 | Saint James Community Hospital and Cancer Treatment Center | Butte | Montana | United States | 59701 |
| 495 | Benefis Healthcare- Sletten Cancer Institute | Great Falls | Montana | United States | 59405 |
| 496 | Berdeaux, Donald MD (UIA Investigator) | Great Falls | Montana | United States | 59405 |
| 497 | Big Sky Oncology | Great Falls | Montana | United States | 59405 |
| 498 | Great Falls Clinic | Great Falls | Montana | United States | 59405 |
| 499 | Saint Peter's Community Hospital | Helena | Montana | United States | 59601 |
| 500 | Glacier Oncology PLLC | Kalispell | Montana | United States | 59901 |
| 501 | Kalispell Medical Oncology | Kalispell | Montana | United States | 59901 |
| 502 | Kalispell Regional Medical Center | Kalispell | Montana | United States | 59901 |
| 503 | Eastern Montana Cancer Center | Miles City | Montana | United States | 59301 |
| 504 | Community Medical Hospital | Missoula | Montana | United States | 59801 |
| 505 | Montana Cancer Specialists | Missoula | Montana | United States | 59802 |
| 506 | Saint Patrick Hospital - Community Hospital | Missoula | Montana | United States | 59802 |
| 507 | Fremont Area Medical Center | Fremont | Nebraska | United States | 68025 |
| 508 | Saint Francis Medical Center | Grand Island | Nebraska | United States | 68803 |
| 509 | Good Samaritan Hospital | Kearney | Nebraska | United States | 68847 |
| 510 | Bryan LGH Medical Center West | Lincoln | Nebraska | United States | 68502 |
| 511 | Bryan LGH Medical Center East | Lincoln | Nebraska | United States | 68506 |
| 512 | Lincoln Medical Education Foundation Cancer Resource Center | Lincoln | Nebraska | United States | 68510 |
| 513 | Saint Elizabeth Regional Medical Center | Lincoln | Nebraska | United States | 68510 |
| 514 | Great Plains Regional Medical Center | North Platte | Nebraska | United States | 69101 |
| 515 | Missouri Valley Cancer Consortium CCOP | Omaha | Nebraska | United States | 68106 |
| 516 | Methodist Estabrook Cancer Center | Omaha | Nebraska | United States | 68114 |
| 517 | Alegent Health Immanuel Medical Center | Omaha | Nebraska | United States | 68122 |
| 518 | Alegent Health Bergan Mercy Medical Center | Omaha | Nebraska | United States | 68124 |
| 519 | Creighton University Medical Center | Omaha | Nebraska | United States | 68131 |
| 520 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198-7830 |
| 521 | Midlands Community Hospital | Papillion | Nebraska | United States | 68046 |
| 522 | University Medical Center of Southern Nevada | Las Vegas | Nevada | United States | 89102 |
| 523 | Nevada Cancer Research Foundation CCOP | Las Vegas | Nevada | United States | 89106 |
| 524 | Nevada Cancer Institute | Las Vegas | Nevada | United States | 89135 |
| 525 | New Hampshire Oncology-Hematology PA | Concord | New Hampshire | United States | 03301 |
| 526 | Columbia Parkland Medical Center | Derry | New Hampshire | United States | 03038 |
| 527 | Exeter Hospital | Exeter | New Hampshire | United States | 03833 |
| 528 | New Hampshire Oncology Hematology Associates | Hooksett | New Hampshire | United States | 03106 |
| 529 | Cheshire Medical Center-Dartmouth-Hitchcock Keene | Keene | New Hampshire | United States | 03431 |
| 530 | LRGHealthcare-Lakes Region General Hospital | Laconia | New Hampshire | United States | 03246 |
| 531 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 532 | Elliot Hospital | Manchester | New Hampshire | United States | 03103 |
| 533 | Portsmouth Regional Hospital | Portsmouth | New Hampshire | United States | 03802 |
| 534 | Ocean Medical Center | Brick | New Jersey | United States | 08724 |
| 535 | Cooper Hospital University Medical Center | Camden | New Jersey | United States | 08103 |
| 536 | Veterans Adminstration New Jersey Health Care System | East Orange | New Jersey | United States | 07018-1095 |
| 537 | Englewood Hospital and Medical Center | Englewood | New Jersey | United States | 07631 |
| 538 | Hunterdon Medical Center | Flemington | New Jersey | United States | 08822 |
| 539 | CentraState Medical Center | Freehold | New Jersey | United States | 07728 |
| 540 | Cancer Institute of New Jersey At Hamilton | Hamilton | New Jersey | United States | 08690 |
| 541 | Saint Barnabas Medical Center | Livingston | New Jersey | United States | 07039 |
| 542 | Monmouth Medical Center | Long Branch | New Jersey | United States | 07740 |
| 543 | Mountainside Hospital | Montclair | New Jersey | United States | 07042 |
| 544 | Morristown Memorial Hospital | Morristown | New Jersey | United States | 07962 |
| 545 | Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County | Mount Holly | New Jersey | United States | 08060 |
| 546 | Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
| 547 | Warren Hospital | Phillipsburg | New Jersey | United States | 08865 |
| 548 | Booker Cancer Center at Riverview Medical Center | Red Bank | New Jersey | United States | 07701 |
| 549 | Somerset Medical Center | Somerville | New Jersey | United States | 08876 |
| 550 | Sparta Cancer Treatment Center | Sparta | New Jersey | United States | 07871 |
| 551 | Overlook Hospital | Summit | New Jersey | United States | 07902 |
| 552 | South Jersey Healthcare | Vineland | New Jersey | United States | 08360 |
| 553 | Virtua West Jersey Hospital Voorhees | Voorhees | New Jersey | United States | 08043 |
| 554 | University of New Mexico at Lovelace Medical Center | Albuquerque | New Mexico | United States | 87102 |
| 555 | Hematology Oncology Associates | Albuquerque | New Mexico | United States | 87106 |
| 556 | University of New Mexico | Albuquerque | New Mexico | United States | 87106 |
| 557 | New Mexico Oncology Hematology Consultants | Albuquerque | New Mexico | United States | 87109 |
| 558 | Presbyterian Kaseman Hospital | Albuquerque | New Mexico | United States | 87110 |
| 559 | Memorial Medical Center - Las Cruces | Las Cruces | New Mexico | United States | 88011 |
| 560 | New Mexico Cancer Care Associates | Santa Fe | New Mexico | United States | 87505 |
| 561 | Albert Einstein College of Medicine | Bronx | New York | United States | 10461 |
| 562 | The North Division of Montefiore Medical Center | Bronx | New York | United States | 10466 |
| 563 | Montefiore Medical Center | Bronx | New York | United States | 10467-2490 |
| 564 | Long Island College Hospital | Brooklyn | New York | United States | 11201 |
| 565 | Veterans Affairs Western New York Health Care System-Buffalo | Buffalo | New York | United States | 14215 |
| 566 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263 |
| 567 | Mary Imogene Bassett Hospital | Cooperstown | New York | United States | 13326 |
| 568 | Hematology Oncology Associates of Central New York | East Syracuse | New York | United States | 13057 |
| 569 | Adirondack Cancer Center | Glens Falls | New York | United States | 12801 |
| 570 | Catskill Regional Medical Center | Harris | New York | United States | 12742 |
| 571 | Orange Regional Medical Center | Middletown | New York | United States | 10940 |
| 572 | Winthrop University Hospital | Mineola | New York | United States | 11501 |
| 573 | Beth Israel Medical Center | New York | New York | United States | 10003 |
| 574 | New York University Langone Medical Center | New York | New York | United States | 10016 |
| 575 | Saint Luke's Roosevelt Hospital Center - Saint Luke's Division | New York | New York | United States | 10025 |
| 576 | Columbia University Medical Center | New York | New York | United States | 10032 |
| 577 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 578 | Nyack Hospital | Nyack | New York | United States | 10960 |
| 579 | Highland Hospital | Rochester | New York | United States | 14620 |
| 580 | Interlakes Foundation Inc-Rochester | Rochester | New York | United States | 14623 |
| 581 | University of Rochester | Rochester | New York | United States | 14642 |
| 582 | State University of New York Upstate Medical University | Syracuse | New York | United States | 13210 |
| 583 | Faxton-Saint Luke's Healthcare | Utica | New York | United States | 13502 |
| 584 | Dickstein Cancer Treatment Center | White Plains | New York | United States | 10601 |
| 585 | Mission Hospitals Inc | Asheville | North Carolina | United States | 28801 |
| 586 | Alamance Regional Medical Center | Burlington | North Carolina | United States | 27216 |
| 587 | University of North Carolina | Chapel Hill | North Carolina | United States | 27599 |
| 588 | Carolinas Medical Center | Charlotte | North Carolina | United States | 28203 |
| 589 | Gaston Memorial Hospital | Gastonia | North Carolina | United States | 28054 |
| 590 | Southeastern Medical Oncology Center | Goldsboro | North Carolina | United States | 27534 |
| 591 | Wayne Memorial Hospital | Goldsboro | North Carolina | United States | 27534 |
| 592 | Wayne Radiation Oncology | Goldsboro | North Carolina | United States | 27534 |
| 593 | Margaret R Pardee Memorial Hospital | Hendersonville | North Carolina | United States | 28791 |
| 594 | Kinston Medical Specialists PA | Kinston | North Carolina | United States | 28501 |
| 595 | Rutherford Hospital | Rutherfordton | North Carolina | United States | 28139 |
| 596 | Iredell Memorial Hospital | Statesville | North Carolina | United States | 28677 |
| 597 | Marion L Shepard Cancer Center | Washington | North Carolina | United States | 27889 |
| 598 | New Hanover Regional Medical Center | Wilmington | North Carolina | United States | 28401 |
| 599 | Wilson Medical Center | Wilson | North Carolina | United States | 27893 |
| 600 | Bismarck Cancer Center | Bismarck | North Dakota | United States | 58501 |
| 601 | Medcenter One Health Systems | Bismarck | North Dakota | United States | 58501 |
| 602 | Mid Dakota Clinic | Bismarck | North Dakota | United States | 58501 |
| 603 | Saint Alexius Medical Center | Bismarck | North Dakota | United States | 58501 |
| 604 | Veterans Administration Medical Center | Fargo | North Dakota | United States | 58102 |
| 605 | Innovis Health South University | Fargo | North Dakota | United States | 58103 |
| 606 | Meritcare Hospital | Fargo | North Dakota | United States | 58122 |
| 607 | MeritCare Medical Group | Fargo | North Dakota | United States | 58122 |
| 608 | Altru Cancer Center | Grand Forks | North Dakota | United States | 58201 |
| 609 | Trinity Cancer Care Center | Minot | North Dakota | United States | 58701 |
| 610 | Akron City Hospital | Akron | Ohio | United States | 44304 |
| 611 | Akron General Medical Center | Akron | Ohio | United States | 44307 |
| 612 | Summa Barberton Hospital | Barberton | Ohio | United States | 44203 |
| 613 | Mary Rutan Hospital | Bellefontaine | Ohio | United States | 43311 |
| 614 | The Boardman Cancer Center | Boardman | Ohio | United States | 44512 |
| 615 | Wood County Oncology Center | Bowling Green | Ohio | United States | 43402 |
| 616 | Mercy Medical Center | Canton | Ohio | United States | 44708 |
| 617 | Aultman Health Foundation | Canton | Ohio | United States | 44710 |
| 618 | Adena Regional Medical Center | Chillicothe | Ohio | United States | 54601 |
| 619 | Case Western Reserve University | Cleveland | Ohio | United States | 44106 |
| 620 | MetroHealth Medical Center | Cleveland | Ohio | United States | 44109 |
| 621 | Cleveland Clinic Foundation | Cleveland | Ohio | United States | 44195 |
| 622 | Ohio State University Medical Center | Columbus | Ohio | United States | 43210 |
| 623 | Riverside Methodist Hospital | Columbus | Ohio | United States | 43214 |
| 624 | Columbus CCOP | Columbus | Ohio | United States | 43215 |
| 625 | Grant Medical Center | Columbus | Ohio | United States | 43215 |
| 626 | Mount Carmel Health Center West | Columbus | Ohio | United States | 43222 |
| 627 | Doctors Hospital | Columbus | Ohio | United States | 43228 |
| 628 | Grandview Hospital | Dayton | Ohio | United States | 45405 |
| 629 | Good Samaritan Hospital - Dayton | Dayton | Ohio | United States | 45406 |
| 630 | Miami Valley Hospital | Dayton | Ohio | United States | 45409 |
| 631 | Samaritan North Health Center | Dayton | Ohio | United States | 45415 |
| 632 | Veteran Affairs Medical Center | Dayton | Ohio | United States | 45428 |
| 633 | Dayton CCOP | Dayton | Ohio | United States | 45429 |
| 634 | Grady Memorial Hospital | Delaware | Ohio | United States | 43015 |
| 635 | Hematology Oncology Center Incorporated | Elyria | Ohio | United States | 44035 |
| 636 | Blanchard Valley Hospital | Findlay | Ohio | United States | 45840 |
| 637 | Atrium Medical Center-Middletown Regional Hospital | Franklin | Ohio | United States | 45005-1066 |
| 638 | Fremont Memorial Hospital | Fremont | Ohio | United States | 43420 |
| 639 | Wayne Hospital | Greenville | Ohio | United States | 45331 |
| 640 | Cleveland Clinic Cancer Center Independence | Independence | Ohio | United States | 44131 |
| 641 | Cole, Sharon, K. M.D. (UIA Investigator) | Kenton | Ohio | United States | 43326 |
| 642 | Kettering Medical Center | Kettering | Ohio | United States | 45429 |
| 643 | Fairfield Medical Center | Lancaster | Ohio | United States | 43130 |
| 644 | Saint Rita's Medical Center | Lima | Ohio | United States | 45801 |
| 645 | Lima Memorial Hospital | Lima | Ohio | United States | 45804 |
| 646 | Mansfield General Hospital-MedCentral Health System | Mansfield | Ohio | United States | 44903 |
| 647 | Marietta Memorial Hospital | Marietta | Ohio | United States | 45750 |
| 648 | Northwest Ohio Oncology Center | Maumee | Ohio | United States | 43537-1839 |
| 649 | Saint Luke's Hospital | Maumee | Ohio | United States | 43537 |
| 650 | Toledo Radiation Oncology at Northwest Ohio Onocolgy Center | Maumee | Ohio | United States | 43537 |
| 651 | Licking Memorial Hospital | Newark | Ohio | United States | 43055 |
| 652 | Bayview Oncology Associates | Oregon | Ohio | United States | 43616 |
| 653 | Saint Charles Hospital | Oregon | Ohio | United States | 43616 |
| 654 | Cancer Care Center, Incorporated | Salem | Ohio | United States | 44460 |
| 655 | Firelands Regional Medical Center | Sandusky | Ohio | United States | 44870 |
| 656 | North Coast Cancer Care | Sandusky | Ohio | United States | 44870 |
| 657 | Community Hospital Springfield | Springfield | Ohio | United States | 45505 |
| 658 | Flower Memorial Hospital | Sylvania | Ohio | United States | 43560 |
| 659 | Mercy Hospital of Tiffin | Tiffin | Ohio | United States | 44883 |
| 660 | The Toledo Hospital | Toledo | Ohio | United States | 43606 |
| 661 | Saint Vincent Mercy Medical Center | Toledo | Ohio | United States | 43608 |
| 662 | University of Toledo | Toledo | Ohio | United States | 43614 |
| 663 | Toledo Community Hospital Oncology Program CCOP | Toledo | Ohio | United States | 43617 |
| 664 | Mercy Cancer Center at Saint Anne Mercy Hospital | Toledo | Ohio | United States | 43623 |
| 665 | Toledo Clinic | Toledo | Ohio | United States | 43623 |
| 666 | Upper Valley Medical Center | Troy | Ohio | United States | 45373 |
| 667 | Saint Joseph Cancer Center | Warren | Ohio | United States | 44484 |
| 668 | Fulton County Health Center | Wauseon | Ohio | United States | 43567 |
| 669 | Saint Ann's Hospital | Westerville | Ohio | United States | 43081 |
| 670 | Clinton Memorial Hospital | Wilmington | Ohio | United States | 45177 |
| 671 | Cancer Treatment Center | Wooster | Ohio | United States | 44691 |
| 672 | Cleveland Clinic Wooster Specialty Center | Wooster | Ohio | United States | 44691 |
| 673 | Wright-Patterson Medical Center | Wright-Patterson Air Force Base | Ohio | United States | 45433-5529 |
| 674 | Greene Memorial Hospital | Xenia | Ohio | United States | 45385 |
| 675 | Saint Elizabeth Hospital Medical Center | Youngstown | Ohio | United States | 44501 |
| 676 | Genesis HealthCare System | Zanesville | Ohio | United States | 43701 |
| 677 | Cancer Centers of Southwest Oklahoma Research - Lawton | Lawton | Oklahoma | United States | 73505 |
| 678 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 679 | Cancer Care Associates | Oklahoma City | Oklahoma | United States | 73120 |
| 680 | Natalie W Bryant Cancer Center | Tulsa | Oklahoma | United States | 74136 |
| 681 | Bay Area Hospital | Coos Bay | Oregon | United States | 97420 |
| 682 | Legacy Mount Hood Medical Center | Gresham | Oregon | United States | 97030 |
| 683 | Providence Milwaukie Hospital | Milwaukie | Oregon | United States | 97222 |
| 684 | Legacy Good Samaritan Hospital and Medical Center | Portland | Oregon | United States | 97210 |
| 685 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
| 686 | Adventist Medical Center | Portland | Oregon | United States | 97216 |
| 687 | Columbia River Oncology Program | Portland | Oregon | United States | 97225 |
| 688 | Providence Saint Vincent Medical Center | Portland | Oregon | United States | 97225 |
| 689 | Legacy Emanuel Hospital and Health Center | Portland | Oregon | United States | 97227 |
| 690 | Northwest Cancer Specialists-Rose Quarter Cancer Center | Portland | Oregon | United States | 97227 |
| 691 | Kaiser Permanente | Portland | Oregon | United States | 97232 |
| 692 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 693 | Salem Hospital | Salem | Oregon | United States | 97309 |
| 694 | Legacy Meridian Park Hospital | Tualatin | Oregon | United States | 97062 |
| 695 | Abington Memorial Hospital | Abington | Pennsylvania | United States | 19001 |
| 696 | Lehigh Valley Hospital | Allentown | Pennsylvania | United States | 18105 |
| 697 | Saint Luke's Hospital | Bethlehem | Pennsylvania | United States | 18015 |
| 698 | Bryn Mawr Hospital | Bryn Mawr | Pennsylvania | United States | 19010 |
| 699 | Marion Community Hospital | Carbondale | Pennsylvania | United States | 18407 |
| 700 | Geisinger Medical Center | Danville | Pennsylvania | United States | 17822-2001 |
| 701 | Mercy Fitzgerald Hospital | Darby | Pennsylvania | United States | 19023-1291 |
| 702 | Doylestown Hospital | Doylestown | Pennsylvania | United States | 18901 |
| 703 | Delaware County Memorial Hospital | Drexel Hill | Pennsylvania | United States | 19026 |
| 704 | Pocono Medical Center | East Stroudsburg | Pennsylvania | United States | 18301 |
| 705 | Easton Hospital | Easton | Pennsylvania | United States | 18042 |
| 706 | Ephrata Cancer Center | Ephrata | Pennsylvania | United States | 17522 |
| 707 | PinnacleHealth Regional Cancer Center at Polyclinic Hospital | Harrisburg | Pennsylvania | United States | 17110 |
| 708 | Geisinger South Wilkes Barre-Hazelton Cancer Center | Hazleton | Pennsylvania | United States | 18201 |
| 709 | Lancaster General Hospital | Lancaster | Pennsylvania | United States | 17604 |
| 710 | Central PA Hematology-Medical Oncology Associates PC | Lemoyne | Pennsylvania | United States | 17043 |
| 711 | Riddle Hospital | Media | Pennsylvania | United States | 19063 |
| 712 | Paoli Memorial Hospital | Paoli | Pennsylvania | United States | 19301 |
| 713 | Abramson Cancer Center of The University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 714 | Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 715 | Thomas Jefferson University Hospital | Philadelphia | Pennsylvania | United States | 19107 |
| 716 | Fox Chase Cancer Center | Philadelphia | Pennsylvania | United States | 19111-2497 |
| 717 | Aria Health-Torresdale Campus | Philadelphia | Pennsylvania | United States | 19114 |
| 718 | Albert Einstein Medical Center | Philadelphia | Pennsylvania | United States | 19141 |
| 719 | Allegheny Cancer Center at Allegheny General Hospital | Pittsburgh | Pennsylvania | United States | 15212 |
| 720 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15213 |
| 721 | Western Pennsylvania Hospital | Pittsburgh | Pennsylvania | United States | 15224-1791 |
| 722 | Pottstown Memorial Medical Center | Pottstown | Pennsylvania | United States | 19464 |
| 723 | Saint Joseph Medical Center | Reading | Pennsylvania | United States | 19605 |
| 724 | Guthrie Clinic - Sayre | Sayre | Pennsylvania | United States | 18840 |
| 725 | Mercy Hospital | Scranton | Pennsylvania | United States | 18501 |
| 726 | Hematology and Oncology Associates of North East Pennsylvania | Scranton | Pennsylvania | United States | 18508 |
| 727 | Community Medical Center | Scranton | Pennsylvania | United States | 18510 |
| 728 | Moses Taylor Hospital | Scranton | Pennsylvania | United States | 18510 |
| 729 | Scranton Hematology Oncology | Scranton | Pennsylvania | United States | 18510 |
| 730 | Grand View Hospital | Sellersville | Pennsylvania | United States | 18960 |
| 731 | Geisinger Medical Group | State College | Pennsylvania | United States | 16801 |
| 732 | Mount Nittany Medical Center | State College | Pennsylvania | United States | 16803 |
| 733 | Associates In Hematology Oncology PC-Upland | Upland | Pennsylvania | United States | 19013 |
| 734 | Jennersville Regional Hospital | West Grove | Pennsylvania | United States | 19390 |
| 735 | Reading Hospital and Medical Center | West Reading | Pennsylvania | United States | 19612 |
| 736 | Geisinger Wyoming Valley | Wilkes-Barre | Pennsylvania | United States | 18711 |
| 737 | Lankenau Hospital | Wynnewood | Pennsylvania | United States | 19096 |
| 738 | Mainline Health CCOP | Wynnewood | Pennsylvania | United States | 19096 |
| 739 | Hematology and Oncology Associates of Rhode Island Inc | Cranston | Rhode Island | United States | 02920 |
| 740 | Rhode Island Hospital | Providence | Rhode Island | United States | 02903 |
| 741 | Miriam Hospital | Providence | Rhode Island | United States | 02906 |
| 742 | Kent County Hospital | Warwick | Rhode Island | United States | 02886 |
| 743 | AnMed Health Hospital | Anderson | South Carolina | United States | 29621 |
| 744 | Medical University of South Carolina | Charleston | South Carolina | United States | 29425 |
| 745 | Greenville Memorial Hospital | Greenville | South Carolina | United States | 29605 |
| 746 | Greenville CCOP | Greenville | South Carolina | United States | 29615 |
| 747 | Spartanburg Regional Medical Center | Spartanburg | South Carolina | United States | 29303 |
| 748 | Upstate Carolina CCOP | Spartanburg | South Carolina | United States | 29303 |
| 749 | Conklin Regional Cancer Center | Aberdeen | South Dakota | United States | 57401 |
| 750 | Rapid City Regional Hospital | Rapid City | South Dakota | United States | 57701 |
| 751 | Sanford Cancer Center-Oncology Clinic | Sioux Falls | South Dakota | United States | 57104 |
| 752 | Avera Cancer Institute | Sioux Falls | South Dakota | United States | 57105 |
| 753 | Avera McKennan Hospital and University Health Center | Sioux Falls | South Dakota | United States | 57105 |
| 754 | Medical X-Ray Center | Sioux Falls | South Dakota | United States | 57105 |
| 755 | Sanford University of South Dakota Medical Center | Sioux Falls | South Dakota | United States | 57117-5134 |
| 756 | Wellmont Holston Valley Hospital and Medical Center | Kingsport | Tennessee | United States | 37660 |
| 757 | Thompson Cancer Survival Center | Knoxville | Tennessee | United States | 37916 |
| 758 | Veterans Affairs Medical Center - Memphis | Memphis | Tennessee | United States | 38104 |
| 759 | Tennessee Oncology PLLC- Centennial Medical Center | Nashville | Tennessee | United States | 37203 |
| 760 | Meharry Medical College | Nashville | Tennessee | United States | 37208-3599 |
| 761 | Vanderbilt University | Nashville | Tennessee | United States | 37232 |
| 762 | The Don and Sybil Harrington Cancer Center | Amarillo | Texas | United States | 79106 |
| 763 | Texas Health Presbyterian Hospital Dallas | Dallas | Texas | United States | 75231 |
| 764 | The Center for Integrative Cancer Medicine | El Paso | Texas | United States | 79902 |
| 765 | Brooke Army Medical Center | Fort Sam Houston | Texas | United States | 78234 |
| 766 | University of Texas Medical Branch | Galveston | Texas | United States | 77555-0565 |
| 767 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 768 | Ben Taub General Hospital | Houston | Texas | United States | 77030 |
| 769 | Methodist Hospital | Houston | Texas | United States | 77030 |
| 770 | Saint Luke's Episcopal Hospital | Houston | Texas | United States | 77030 |
| 771 | Veterans Administration Medical Center | Houston | Texas | United States | 77030 |
| 772 | Wilford Hall Medical Center | Lackland Air Force Base | Texas | United States | 78236 |
| 773 | Doctor's Hospital of Laredo | Laredo | Texas | United States | 78041 |
| 774 | Audie L Murphy Veterans Affairs Hospital | San Antonio | Texas | United States | 78209 |
| 775 | University of Texas Health Science Center | San Antonio | Texas | United States | 78229-3900 |
| 776 | Cancer Therapy and Research Center at The UT Health Science Center at San Antonio | San Antonio | Texas | United States | 78229 |
| 777 | South Texas Oncology and Hematology PA | San Antonio | Texas | United States | 78229 |
| 778 | University Hospital | San Antonio | Texas | United States | 78229 |
| 779 | Scott and White Memorial Hospital | Temple | Texas | United States | 76508 |
| 780 | Southwestern Oncology Research Department | Bennington | Vermont | United States | 05201 |
| 781 | University of Vermont | Burlington | Vermont | United States | 05401 |
| 782 | Danville Regional Medical Center | Danville | Virginia | United States | 24541 |
| 783 | Fredericksburg Oncology Inc | Fredericksburg | Virginia | United States | 22401 |
| 784 | Riverside Middle Peninsula Cancer Center | Gloucester | Virginia | United States | 23061 |
| 785 | Lynchburg Hematology-Oncology Clinic | Lynchburg | Virginia | United States | 24501 |
| 786 | Peninsula Cancer Institute-Newport News | Newport News | Virginia | United States | 23601 |
| 787 | Southwest VA Regional Cancer Center | Norton | Virginia | United States | 24273 |
| 788 | Peninsula Cancer Institute | Williamsburg | Virginia | United States | 23185 |
| 789 | Auburn Regional Medical Center | Auburn | Washington | United States | 98002 |
| 790 | Saint Joseph Hospital | Bellingham | Washington | United States | 98225 |
| 791 | Harrison Bremerton Hematology and Oncology | Bremerton | Washington | United States | 98310 |
| 792 | Providence Centralia Hospital | Centralia | Washington | United States | 98531 |
| 793 | Saint Francis Hospital | Federal Way | Washington | United States | 98003 |
| 794 | Columbia Basin Hematology and Oncology PLLC | Kennewick | Washington | United States | 99336 |
| 795 | Evergreen Hospital Medical Center | Kirkland | Washington | United States | 98033 |
| 796 | Providence - Saint Peter Hospital | Olympia | Washington | United States | 98506-5166 |
| 797 | Capital Medical Center | Olympia | Washington | United States | 98507 |
| 798 | Olympic Medical Center | Port Angeles | Washington | United States | 98362 |
| 799 | Good Samaritan Community Hospital | Puyallup | Washington | United States | 98372 |
| 800 | Valley Medical Center | Renton | Washington | United States | 98055 |
| 801 | Virginia Mason CCOP | Seattle | Washington | United States | 98101 |
| 802 | Minor and James Medical PLLC | Seattle | Washington | United States | 98104 |
| 803 | Puget Sound Oncology Consortium | Seattle | Washington | United States | 98109 |
| 804 | Group Health Cooperative | Seattle | Washington | United States | 98112 |
| 805 | Swedish Medical Center-First Hill | Seattle | Washington | United States | 98122-4307 |
| 806 | The Polyclinic | Seattle | Washington | United States | 98122 |
| 807 | University of Washington Medical Center | Seattle | Washington | United States | 98195 |
| 808 | Cancer Care Northwest - Spokane South | Spokane | Washington | United States | 99202 |
| 809 | Sacred Heart Medical Center | Spokane | Washington | United States | 99204 |
| 810 | Holy Family Hospital | Spokane | Washington | United States | 99207 |
| 811 | Allenmore Hospital | Tacoma | Washington | United States | 98405 |
| 812 | Northwest CCOP | Tacoma | Washington | United States | 98405 |
| 813 | Saint Joseph Medical Center | Tacoma | Washington | United States | 98405 |
| 814 | Tacoma General Hospital | Tacoma | Washington | United States | 98405 |
| 815 | Multicare Health System | Tacoma | Washington | United States | 98415 |
| 816 | Saint Clare Hospital | Tacoma | Washington | United States | 98499 |
| 817 | Southwest Washington Medical Center | Vancouver | Washington | United States | 98668 |
| 818 | North Star Lodge Cancer Center at Yakima Valley Memorial Hospital | Yakima | Washington | United States | 98902 |
| 819 | Edwards Comprehensive Cancer Center | Huntington | West Virginia | United States | 25701 |
| 820 | West Virginia University | Morgantown | West Virginia | United States | 26506 |
| 821 | Camden-Clark Memorial Hospital | Parkersburg | West Virginia | United States | 26101 |
| 822 | Princeton Community Hospital | Princeton | West Virginia | United States | 24740 |
| 823 | Wheeling Hospital | Wheeling | West Virginia | United States | 26003 |
| 824 | Langlade Hospital and Cancer Center | Antigo | Wisconsin | United States | 54409 |
| 825 | Marshfield Clinic Cancer Care at Regional Cancer Center | Eau Claire | Wisconsin | United States | 54701 |
| 826 | Sacred Heart Hospital | Eau Claire | Wisconsin | United States | 54701 |
| 827 | Midelfort Clinic-Clairemont Campus | Eau Claire | Wisconsin | United States | 54702 |
| 828 | Mayo Clinic Health System Eau Claire Hospital - Luther Campus | Eau Claire | Wisconsin | United States | 54703 |
| 829 | Central Wisconsin Cancer Program | Fond Du Lac | Wisconsin | United States | 54935 |
| 830 | Green Bay Oncology at Saint Vincent Hospital | Green Bay | Wisconsin | United States | 54301-3526 |
| 831 | Saint Vincent Hospital | Green Bay | Wisconsin | United States | 54301 |
| 832 | Green Bay Oncology Limited at Saint Mary's Hospital | Green Bay | Wisconsin | United States | 54303 |
| 833 | Saint Mary's Hospital | Green Bay | Wisconsin | United States | 54303 |
| 834 | Aurora BayCare Medical Center | Green Bay | Wisconsin | United States | 54311-6519 |
| 835 | Mercy Health System | Janesville | Wisconsin | United States | 53547 |
| 836 | UW Cancer Center Johnson Creek | Johnson Creek | Wisconsin | United States | 53038 |
| 837 | Franciscan Skemp Healthcare | La Crosse | Wisconsin | United States | 54601 |
| 838 | UW Health Oncology - 1 South Park | Madison | Wisconsin | United States | 53715 |
| 839 | Dean Hematology and Oncology Clinic | Madison | Wisconsin | United States | 53717 |
| 840 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 841 | Bay Area Medical Center | Marinette | Wisconsin | United States | 54143 |
| 842 | Vince Lombardi Cancer Clinic-Marinette | Marinette | Wisconsin | United States | 54143 |
| 843 | Marshfield Clinic | Marshfield | Wisconsin | United States | 54449 |
| 844 | Saint Joseph's Hospital | Marshfield | Wisconsin | United States | 54449 |
| 845 | Marshfield Clinic-Minocqua Center | Minocqua | Wisconsin | United States | 54548 |
| 846 | Oconomowoc Memorial Hospital-ProHealth Care Inc | Oconomowoc | Wisconsin | United States | 53066-3896 |
| 847 | Green Bay Oncology - Oconto Falls | Oconto Falls | Wisconsin | United States | 54154 |
| 848 | Marshfield Clinic at James Beck Cancer Center | Rhinelander | Wisconsin | United States | 54501 |
| 849 | Marshfield Clinic-Rice Lake Center | Rice Lake | Wisconsin | United States | 54868 |
| 850 | Saint Michael's Hospital | Stevens Point | Wisconsin | United States | 54481 |
| 851 | Green Bay Oncology - Sturgeon Bay | Sturgeon Bay | Wisconsin | United States | 54235 |
| 852 | Waukesha Memorial Hospital | Waukesha | Wisconsin | United States | 53188 |
| 853 | Aspirus Regional Cancer Center | Wausau | Wisconsin | United States | 54401 |
| 854 | Marshfield Clinic-Wausau Center | Wausau | Wisconsin | United States | 54401 |
| 855 | Diagnostic and Treatment Center | Weston | Wisconsin | United States | 54476 |
| 856 | Marshfield Clinic - Weston Center | Weston | Wisconsin | United States | 54476 |
| 857 | Marshfield Clinic - Wisconsin Rapids Center | Wisconsin Rapids | Wisconsin | United States | 54494 |
| 858 | Welch Cancer Center | Sheridan | Wyoming | United States | 82801 |
| 859 | Tom Baker Cancer Centre | Calgary | Alberta | Canada | T2N 4N2 |
| 860 | Cross Cancer Institute | Edmonton | Alberta | Canada | T6G 1Z2 |
| 861 | Lions Gate Hospital | North Vancouver | British Columbia | Canada | V7L 2L7 |
| 862 | BCCA-Fraser Valley Cancer Centre | Surrey | British Columbia | Canada | V3V 1Z2 |
| 863 | BCCA-Vancouver Cancer Centre | Vancouver | British Columbia | Canada | V5Z 4E6 |
| 864 | CancerCare Manitoba | Winnipeg | Manitoba | Canada | R3E 0V9 |
| 865 | The Moncton Hospital | Moncton | New Brunswick | Canada | E1C 6Z8 |
| 866 | Atlantic Health Sciences Corporation-Saint John Regional Hospital | Saint John | New Brunswick | Canada | E2L 4L2 |
| 867 | The Royal Victoria Hospital | Barrie | Ontario | Canada | L4M 6M2 |
| 868 | Cambridge Memorial Hospital | Cambridge | Ontario | Canada | N1R 3G2 |
| 869 | Juravinski Cancer Centre at Hamilton Health Sciences | Hamilton | Ontario | Canada | L8V 5C2 |
| 870 | Cancer Centre of Southeastern Ontario at Kingston General Hospital | Kingston | Ontario | Canada | K7L 5P9 |
| 871 | Grand River Regional Cancer Centre at Grand River Hospital | Kitchener | Ontario | Canada | N2G 1G3 |
| 872 | London Regional Cancer Program | London | Ontario | Canada | N6A 4L6 |
| 873 | Credit Valley Hospital | Mississauga | Ontario | Canada | L5M 2N1 |
| 874 | Ottawa Health Research Institute-General Division | Ottawa | Ontario | Canada | K1H 1C4 |
| 875 | Algoma District Cancer Program Sault Area Hospital | Sault Ste Marie | Ontario | Canada | P6A 3C4 |
| 876 | Niagara Health System-Saint Catharines General | St. Catharines | Ontario | Canada | L2R 2Z7 |
| 877 | Regional Cancer Program of The Hopital Regional de Sudbury Regional Hopital | Sudbury | Ontario | Canada | P3E 5J1 |
| 878 | Thunder Bay Regional Health Science Centre | Thunder Bay | Ontario | Canada | P7B 6V4 |
| 879 | Toronto East General Hospital | Toronto | Ontario | Canada | M4C 3E7 |
| 880 | Odette Cancer Centre- Sunnybrook Health Sciences Centre | Toronto | Ontario | Canada | M4N 3M5 |
| 881 | Saint Michael's Hospital | Toronto | Ontario | Canada | M5B 1W8 |
| 882 | Mount Sinai Hospital | Toronto | Ontario | Canada | M5G 1X5 |
| 883 | University Health Network-Princess Margaret Hospital | Toronto | Ontario | Canada | M5G 2M9 |
| 884 | Trillium Health Centre-West Toronto | Toronto | Ontario | Canada | M9C 1A5 |
| 885 | Windsor Regional Cancer Centre | Windsor | Ontario | Canada | N8W 2X3 |
| 886 | PEI Cancer Treatment Centre-Queen Elizabeth Hospital | Charlottetown | Prince Edward Island | Canada | C1A 8T5 |
| 887 | McGill University Department of Oncology | Montreal | Quebec | Canada | H2W 1S6 |
| 888 | Allan Blair Cancer Centre | Regina | Saskatchewan | Canada | S4T 7T1 |
| 889 | Saskatoon Cancer Centre | Saskatoon | Saskatchewan | Canada | S7N 4H4 |
| 890 | Andres Grillasca Hospital | Ponce | Puerto Rico | 00733 | |
| 891 | Hato Rey Hematology Oncology Group | San Juan | Puerto Rico | 00917 | |
| 892 | I Gonzales Martinez-Oncologic Hospital | San Juan | Puerto Rico | 00919 | |
| 893 | San Juan Veterans Affairs Medical Center | San Juan | Puerto Rico | 00921-3201 | |
| 894 | San Juan City Hospital | San Juan | Puerto Rico | 00928 |
Sponsors and Collaborators
- National Cancer Institute (NCI)
- Eastern Cooperative Oncology Group
Investigators
- Principal Investigator: Steven A Alberts, MD, North Central Cancer Treatment Group
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079274
Other Study ID Numbers:
- NCI-2009-00639
- N0147
- U10CA025224
- CDR0000355132
- NCT00170092
First Posted:
Mar 10, 2004
Last Update Posted:
May 13, 2020
Last Verified:
Apr 1, 2020
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm A (Combination Chemotherapy) | Arm B (Combination Chemotherapy) | Arm C (Combination Chemotherapy) | Arm D (Combination Chemotherapy, Monoclonal Antibody) | Arm E (Combination Chemotherapy, Monoclonal Antibody) | Arm F (Combination Chemotherapy, Monoclonal Antibody) | Arm G (Locally Directed Therapy) |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients received irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients received the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients received cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients received cetuximab as in arm D and irinotecan, leucovorin calcium, and fluorouracil as in arm B. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV leucovorin calcium: Given IV fluorouracil: Given I cetuximab: Given IV | Patients received cetuximab as in arm D and chemotherapy as in arm C. irinotecan hydrochloride: Given IV oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients determined to have mutated Kirsten rat sarcoma (KRAS) (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists. Locally Directed Therapy: Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists. |
| Period Title: Overall Study | |||||||
| STARTED | 1402 | 111 | 111 | 1350 | 45 | 46 | 332 |
| COMPLETED | 1081 | 84 | 84 | 906 | 30 | 26 | 332 |
| NOT COMPLETED | 321 | 27 | 27 | 444 | 15 | 20 | 0 |
Baseline Characteristics
| Arm/Group Title | Arm A (Combination Chemotherapy) | Arm B (Combination Chemotherapy) | Arm C (Combination Chemotherapy) | Arm D (Combination Chemotherapy, Monoclonal Antibody) | Arm E (Combination Chemotherapy, Monoclonal Antibody) | Arm F (Combination Chemotherapy, Monoclonal Antibody) | Arm G (Locally Directed Therapy) | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Patients received oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients received irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients received the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients received cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients received cetuximab as in arm D and irinotecan, leucovorin calcium, and fluorouracil as in arm B. Treatment repeated every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients received cetuximab as in arm D and chemotherapy as in arm C. irinotecan hydrochloride: Given IV oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists. Locally Directed Therapy: Patients determined to have mutated KRAS (or KRAS not evaluable) were assigned to an event monitoring arm in which adjuvant therapy was determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification was the responsibility of the treating oncologists. | Total of all reporting groups |
| Overall Participants | 1402 | 111 | 111 | 1350 | 45 | 46 | 332 | 3397 |
| Age (years) [Median (Full Range) ] | ||||||||
| Median (Full Range) [years] |
58
|
57
|
60
|
58
|
59
|
60.5
|
56
|
58
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
662
47.2%
|
53
47.7%
|
50
45%
|
647
47.9%
|
20
44.4%
|
21
45.7%
|
160
48.2%
|
1613
47.5%
|
| Male |
740
52.8%
|
58
52.3%
|
61
55%
|
703
52.1%
|
25
55.6%
|
25
54.3%
|
172
51.8%
|
1784
52.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
| Hispanic or Latino |
64
4.6%
|
5
4.5%
|
3
2.7%
|
62
4.6%
|
4
8.9%
|
2
4.3%
|
18
5.4%
|
158
4.7%
|
| Not Hispanic or Latino |
1107
79%
|
103
92.8%
|
103
92.8%
|
1060
78.5%
|
38
84.4%
|
41
89.1%
|
225
67.8%
|
2677
78.8%
|
| Unknown or Not Reported |
231
16.5%
|
3
2.7%
|
5
4.5%
|
228
16.9%
|
3
6.7%
|
3
6.5%
|
89
26.8%
|
562
16.5%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
6
0.4%
|
1
0.9%
|
1
0.9%
|
7
0.5%
|
0
0%
|
0
0%
|
1
0.3%
|
16
0.5%
|
| Asian |
66
4.7%
|
4
3.6%
|
2
1.8%
|
62
4.6%
|
3
6.7%
|
0
0%
|
12
3.6%
|
149
4.4%
|
| Native Hawaiian or Other Pacific Islander |
8
0.6%
|
0
0%
|
1
0.9%
|
7
0.5%
|
0
0%
|
0
0%
|
0
0%
|
16
0.5%
|
| Black or African American |
94
6.7%
|
6
5.4%
|
7
6.3%
|
96
7.1%
|
5
11.1%
|
2
4.3%
|
29
8.7%
|
239
7%
|
| White |
1202
85.7%
|
98
88.3%
|
100
90.1%
|
1154
85.5%
|
37
82.2%
|
43
93.5%
|
275
82.8%
|
2909
85.6%
|
| More than one race |
3
0.2%
|
2
1.8%
|
0
0%
|
3
0.2%
|
0
0%
|
0
0%
|
1
0.3%
|
9
0.3%
|
| Unknown or Not Reported |
23
1.6%
|
0
0%
|
0
0%
|
21
1.6%
|
0
0%
|
1
2.2%
|
14
4.2%
|
59
1.7%
|
| Region of Enrollment (participants) [Number] | ||||||||
| United States |
1258
89.7%
|
109
98.2%
|
109
98.2%
|
1224
90.7%
|
44
97.8%
|
46
100%
|
303
91.3%
|
3093
91.1%
|
| Canada |
138
9.8%
|
2
1.8%
|
2
1.8%
|
124
9.2%
|
1
2.2%
|
0
0%
|
28
8.4%
|
295
8.7%
|
| Jamaica |
1
0.1%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0%
|
| Puerto Rico |
5
0.4%
|
0
0%
|
0
0%
|
2
0.1%
|
0
0%
|
0
0%
|
1
0.3%
|
8
0.2%
|
| Positive Nodes (participants) [Number] | ||||||||
| 1-3 |
816
58.2%
|
71
64%
|
70
63.1%
|
790
58.5%
|
29
64.4%
|
28
60.9%
|
203
61.1%
|
2007
59.1%
|
| 4+ |
586
41.8%
|
40
36%
|
41
36.9%
|
560
41.5%
|
16
35.6%
|
18
39.1%
|
129
38.9%
|
1390
40.9%
|
| Tumor Stage (participants) [Number] | ||||||||
| T1 or T2 |
198
14.1%
|
18
16.2%
|
14
12.6%
|
213
15.8%
|
5
11.1%
|
5
10.9%
|
56
16.9%
|
509
15%
|
| T3 |
1046
74.6%
|
78
70.3%
|
93
83.8%
|
983
72.8%
|
35
77.8%
|
39
84.8%
|
214
64.5%
|
2488
73.2%
|
| T4 |
158
11.3%
|
15
13.5%
|
4
3.6%
|
153
11.3%
|
4
8.9%
|
2
4.3%
|
62
18.7%
|
398
11.7%
|
| Not Availabe |
0
0%
|
0
0%
|
0
0%
|
1
0.1%
|
1
2.2%
|
0
0%
|
0
0%
|
2
0.1%
|
| Histologic Grade (participants) [Number] | ||||||||
| High |
357
25.5%
|
25
22.5%
|
28
25.2%
|
345
25.6%
|
10
22.2%
|
12
26.1%
|
60
18.1%
|
837
24.6%
|
| Low |
1045
74.5%
|
86
77.5%
|
83
74.8%
|
1005
74.4%
|
35
77.8%
|
34
73.9%
|
272
81.9%
|
2560
75.4%
|
| KRAS Status (participants) [Number] | ||||||||
| Unknown |
56
4%
|
6
5.4%
|
6
5.4%
|
51
3.8%
|
3
6.7%
|
4
8.7%
|
6
1.8%
|
132
3.9%
|
| Mutant |
391
27.9%
|
33
29.7%
|
43
38.7%
|
345
25.6%
|
15
33.3%
|
13
28.3%
|
326
98.2%
|
1166
34.3%
|
| Wildtype |
955
68.1%
|
72
64.9%
|
62
55.9%
|
954
70.7%
|
27
60%
|
29
63%
|
0
0%
|
2099
61.8%
|
Outcome Measures
| Title | Disease-free Survival (Arms A and D: Wild-type KRAS Patients) |
|---|---|
| Description | The primary endpoint for this study was to compare the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier. |
| Time Frame | At 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed using intention to treat principles. All patients that were wild-type KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint. |
| Arm/Group Title | Wild-type KRAS Arm A | Wild-type KRAS Arm D |
|---|---|---|
| Arm/Group Description | Patients from Arm A (and a few patients from Arm C that did not receive irinotecan) that are wild-type KRAS and concurrently randomized with Arm D patients. | Patients from Arm D (and a few patients from Arm F that did not receive irinotecan) that are wild-type KRAS and concurrently randomized with Arm A patients. |
| Measure Participants | 909 | 954 |
| Number (95% Confidence Interval) [percentage of participants] |
74.6
5.3%
|
71.5
64.4%
|
| Title | Disease-free Survival (Arms A and D: Mutant KRAS Patients) |
|---|---|
| Description | A secondary endpoint for this study was to investigate the disease-free survival (DFS) in patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. Disease-free survival is defined as the time from randomization until tumor recurrence or death, whichever is first. Estimated by the method of Kaplan and Meier. |
| Time Frame | At 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed using intention to treat principles. All patients that were KRAS mutant (or not evaluable for KRAS) and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint. |
| Arm/Group Title | Mutant KRAS Arm A | Mutant KRAS Arm D |
|---|---|---|
| Arm/Group Description | Patients from Arm A (and a few patients from Arm C that did not receive irinotecan) that are mutant KRAS and concurrently randomized with Arm D patients. | Patients from Arm D (and a few patients from Arm F that did not receive irinotecan) that are mutant KRAS and concurrently randomized with Arm A patients. |
| Measure Participants | 374 | 343 |
| Number (95% Confidence Interval) [percentage of participants] |
67.1
4.8%
|
65.0
58.6%
|
| Title | Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Wild-type KRAS Patients) |
|---|---|
| Description | Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event free rates (percentage) are reported below for Wild-type KRAS Patients. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed using intention to treat principles. All patients that were wild-type KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint. |
| Arm/Group Title | Wild-type KRAS Arm A | Wild-type KRAS Arm D |
|---|---|---|
| Arm/Group Description | Patients from Arm A (and a few patients from Arm C that did not receive irinotecan) that are wild-type KRAS and concurrently randomized with Arm D patients. | Patients from Arm D (and a few patients from Arm F that did not receive irinotecan) that are wild-type KRAS and concurrently randomized with Arm A patients. |
| Measure Participants | 909 | 954 |
| Number (95% Confidence Interval) [percentage of participants] |
87.3
6.2%
|
85.6
77.1%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Wild-type KRAS Arm A, Wild-type KRAS Arm D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.15 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | HR and p-value reported from a multivariate Cox PH regression model, adjusted for number of nodes, histologic grade, and T stage. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.25 | |
| Confidence Interval |
(2-Sided) 95% 0.92 to 1.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Overall Survival as Measured by the 3-year Event-free Rate (Arms A and D: Mutant KRAS Patients) |
|---|---|
| Description | Evidence of death from any cause within 3 years counted as events in the time to event- Kaplan Meier analysis of overall survival for patients with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). Participants treated according to Arms B, C, E, and F treatment schedules received treatment which included irinotecan hydrochloride and therefore were not analyzed for this endpoint. The 3-year event-free rates (percentage) are report below for mutant KRAS patients. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis was performed using intention to treat principles. All patients that were KRAS mutant (or not evaluable for KRAS) and received randomized treatment according to the Arm A or Arm D intervention schedule were evaluated for this endpoint. Any patient receiving irinotecan was not included in the evaluation of this endpoint. |
| Arm/Group Title | Mutant KRAS Arm A | Mutant KRAS Arm D |
|---|---|---|
| Arm/Group Description | Patients from Arm A (and a few patients from Arm C that did not receive irinotecan) that are mutant KRAS and concurrently randomized with Arm D patients. | Patients from Arm D (and a few patients from Arm F that did not receive irinotecan) that are mutant KRAS and concurrently randomized with Arm A patients. |
| Measure Participants | 374 | 343 |
| Number (95% Confidence Interval) [percentage of participants] |
87.9
6.3%
|
82.7
74.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Wild-type KRAS Arm A, Wild-type KRAS Arm D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.25 |
| Comments | ||
| Method | Regression, Cox | |
| Comments | HR and p-value reported from a multivariate Cox PH regression model, adjusted for number of nodes, histologic grade, and T stage. | |
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 1.27 | |
| Confidence Interval |
(2-Sided) 95% 0.85 to 1.92 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Wild-type KRAS Patients) |
|---|---|
| Description | The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS wild-type randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below. |
| Time Frame | Assessed up to 8 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were wild-type KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule and completed the adverse event form at least once were evaluated for this endpoint. |
| Arm/Group Title | Wild-type KRAS Arm A | Wild-type KRAS Arm D |
|---|---|---|
| Arm/Group Description | Patients from Arm A (and a few patients from Arm C that did not receive irinotecan) that are wild-type KRAS and concurrently randomized with Arm D patients. | Patients from Arm D (and a few patients from Arm F that did not receive irinotecan) that are wild-type KRAS and concurrently randomized with Arm A patients. |
| Measure Participants | 894 | 931 |
| Number [percentage of patients] |
51.1
|
73.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Wild-type KRAS Arm A, Wild-type KRAS Arm D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared | |
| Comments | two-sided chi-squared test | |
| Title | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (v3) (Arms A and D: Mutant KRAS Patients) |
|---|---|
| Description | The maximum grade for each type of toxicity will be recorded for each patient with stage III colon cancer who are KRAS mutant (or KRAS-nonevaluable) and randomized to one of two treatment regimens: 1) oxaliplatin, leucovorin calcium, and fluorouracil (Arm A) or 2) oxaliplatin, leucovorin calcium, fluorouracil and cetuximab (Arm D). The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below. |
| Time Frame | Assessed up to 8 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All patients that were mutant KRAS and received randomized treatment according to the Arm A or Arm D intervention schedule and completed the adverse event form at least once were evaluated for this endpoint. |
| Arm/Group Title | Mutant KRAS Arm A | Mutant KRAS Arm D |
|---|---|---|
| Arm/Group Description | Patients from Arm A (and a few patients from Arm C that did not receive irinotecan) that are mutant KRAS and concurrently randomized with Arm D patients. | Patients from Arm D (and a few patients from Arm F that did not receive irinotecan) that are mutant KRAS and concurrently randomized with Arm A patients. |
| Measure Participants | 367 | 342 |
| Number [percentage of patients] |
55.6
|
72.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Wild-type KRAS Arm A, Wild-type KRAS Arm D |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared | |
| Comments | Two-sided chi-squared test | |
Adverse Events
| Time Frame | 6 months or during treatment | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | All patients that received protocol treatment and completed at least one adverse event assessment are included in this analysis. Adverse event data was not collected for Arm G patients. | |||||||||||||
| Arm/Group Title | Arm A (Combination Chemotherapy) | Arm B (Combination Chemotherapy) | Arm C (Combination Chemotherapy) | Arm D (Combination Chemotherapy, Monoclonal Antibody) | Arm E (Combination Chemotherapy, Monoclonal Antibody) | Arm F (Combination Chemotherapy, Monoclonal Antibody) | Arm G (Locally Directed Therapy) | |||||||
| Arm/Group Description | Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV continuously over 46-48 hours on days 1. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients receive irinotecan IV over 2 hours on day 1 and leucovorin calcium and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients receive the same treatment as in arm A for 6 courses followed by the same treatment as in arm B for 6 courses (total of 12 courses). Treatment continues in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV | Patients receive cetuximab IV over 1 hour on days 1 and 8 and oxaliplatin, leucovorin calcium, and fluorouracil as in arm A. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients receive cetuximab as in arm D and irinotecan, leucovorin calcium, and fluorouracil as in arm B. Treatment repeats every 14 days for up to 12 courses in the absence of unacceptable toxicity or recurrent disease. irinotecan hydrochloride: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients receive cetuximab as in arm D and chemotherapy as in arm C. irinotecan hydrochloride: Given IV oxaliplatin: Given IV leucovorin calcium: Given IV fluorouracil: Given IV cetuximab: Given IV | Patients determined to have mutated KRAS (or KRAS not evaluable) will be assigned to an event monitoring arm in which adjuvant therapy will be determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification will be the responsibility of the treating oncologists. Locally Directed Therapy: Patients determined to have mutated KRAS (or KRAS not evaluable) will be assigned to an event monitoring arm in which adjuvant therapy will be determined and assigned by the treating oncologist. The determination of the type of therapy, duration of treatment, and dose modification will be the responsibility of the treating oncologists. | |||||||
All Cause Mortality |
||||||||||||||
| Arm A (Combination Chemotherapy) | Arm B (Combination Chemotherapy) | Arm C (Combination Chemotherapy) | Arm D (Combination Chemotherapy, Monoclonal Antibody) | Arm E (Combination Chemotherapy, Monoclonal Antibody) | Arm F (Combination Chemotherapy, Monoclonal Antibody) | Arm G (Locally Directed Therapy) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| Arm A (Combination Chemotherapy) | Arm B (Combination Chemotherapy) | Arm C (Combination Chemotherapy) | Arm D (Combination Chemotherapy, Monoclonal Antibody) | Arm E (Combination Chemotherapy, Monoclonal Antibody) | Arm F (Combination Chemotherapy, Monoclonal Antibody) | Arm G (Locally Directed Therapy) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 93/1378 (6.7%) | 9/108 (8.3%) | 11/108 (10.2%) | 150/1326 (11.3%) | 4/42 (9.5%) | 5/44 (11.4%) | 0/0 (NaN) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Febrile neutropenia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hemoglobin decreased | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cardiac disorders | ||||||||||||||
| Asystole | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Atrial fibrillation | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 4 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Cardiac disorder | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cardiac pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 1/42 (2.4%) | 1 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Cardiopulmonary arrest | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Left ventricular failure | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Myocardial ischemia | 6/1378 (0.4%) | 7 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 9/1326 (0.7%) | 9 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Premature ventricular contractions | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Sinus tachycardia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Supraventricular tachycardia | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ventricular tachycardia | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ear and labyrinth disorders | ||||||||||||||
| Tinnitus | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastrointestinal disorders | ||||||||||||||
| Abdominal distension | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Abdominal pain | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colitis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colonic fistula | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colonic obstruction | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colonic perforation | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colonic stenosis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Diarrhea | 15/1378 (1.1%) | 15 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 20/1326 (1.5%) | 20 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ear, nose and throat examination abnormal | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Endoscopy small intestine abnormal | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Enteritis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Esophageal hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Esophageal ulcer | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastritis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ileus | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Mucositis oral | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Nausea | 5/1378 (0.4%) | 5 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pancreatitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Rectal hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vomiting | 3/1378 (0.2%) | 3 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| General disorders | ||||||||||||||
| Chest pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Death NOS | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Fatigue | 3/1378 (0.2%) | 3 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 4/1326 (0.3%) | 4 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Sudden death | 0/1378 (0%) | 0 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hepatobiliary disorders | ||||||||||||||
| Cholecystitis | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gallbladder pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hepatobiliary disease | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Immune system disorders | ||||||||||||||
| Hypersensitivity | 6/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 17/1326 (1.3%) | 17 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Infections and infestations | ||||||||||||||
| Abdominal infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Bladder infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Catheter related infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colitis, infectious (e.g., Clostridium difficile) | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Infectious colitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Infectious meningitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pneumonia | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Sepsis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 7/1326 (0.5%) | 7 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Skin infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Urinary tract infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Wound infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||
| Fracture | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Postoperative hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Investigations | ||||||||||||||
| Activated partial thromboplastin time prolonged | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Alanine aminotransferase increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Amylase increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Aspartate aminotransferase increased | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Blood bilirubin increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cardiac troponin I increased | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 2/42 (4.8%) | 2 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cardiac troponin T increased | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Creatine phosphokinase increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Creatinine increased | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| INR increased | 4/1378 (0.3%) | 5 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Lipase increased | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Neutrophil count decreased | 13/1378 (0.9%) | 15 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 8/1326 (0.6%) | 8 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Platelet count decreased | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Weight loss | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Blood glucose increased | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Dehydration | 7/1378 (0.5%) | 7 | 1/108 (0.9%) | 1 | 2/108 (1.9%) | 2 | 10/1326 (0.8%) | 10 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Glucose intolerance | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum calcium decreased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum glucose decreased | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum magnesium decreased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 6/1326 (0.5%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum phosphate decreased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum potassium decreased | 10/1378 (0.7%) | 10 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 20/1326 (1.5%) | 20 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum sodium decreased | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Chest wall pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Muscle weakness | 0/1378 (0%) | 0 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Musculoskeletal disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Myalgia | 0/1378 (0%) | 0 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Myositis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Neck pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pain in extremity | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Nervous system disorders | ||||||||||||||
| Ataxia | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Depressed level of consciousness | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Dizziness | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Encephalopathy | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Headache | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Intracranial hemorrhage | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ischemia cerebrovascular | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Peripheral motor neuropathy | 1/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Peripheral sensory neuropathy | 1/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Seizure | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Speech disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Syncope | 6/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 2/108 (1.9%) | 2 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Psychiatric disorders | ||||||||||||||
| Confusion | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Depression | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Renal and urinary disorders | ||||||||||||||
| Bladder hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ureteric obstruction | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Bronchospasm | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cough | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Dyspnea | 2/1378 (0.1%) | 2 | 1/108 (0.9%) | 1 | 2/108 (1.9%) | 2 | 6/1326 (0.5%) | 6 | 2/42 (4.8%) | 2 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Hypoxia | 2/1378 (0.1%) | 2 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Laryngeal edema | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pleural effusion | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pneumonitis | 2/1378 (0.1%) | 2 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 5 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pneumothorax | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pulmonary fibrosis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Respiratory disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Erythema multiforme | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Masculinization | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Rash acneiform | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Rash desquamating | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vascular disorders | ||||||||||||||
| Hypertension | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hypotension | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Thrombosis | 5/1378 (0.4%) | 5 | 2/108 (1.9%) | 2 | 0/108 (0%) | 0 | 9/1326 (0.7%) | 9 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Arm A (Combination Chemotherapy) | Arm B (Combination Chemotherapy) | Arm C (Combination Chemotherapy) | Arm D (Combination Chemotherapy, Monoclonal Antibody) | Arm E (Combination Chemotherapy, Monoclonal Antibody) | Arm F (Combination Chemotherapy, Monoclonal Antibody) | Arm G (Locally Directed Therapy) | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 688/1378 (49.9%) | 53/108 (49.1%) | 60/108 (55.6%) | 928/1326 (70%) | 26/42 (61.9%) | 33/44 (75%) | 0/0 (NaN) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Febrile neutropenia | 12/1378 (0.9%) | 12 | 2/108 (1.9%) | 3 | 3/108 (2.8%) | 3 | 30/1326 (2.3%) | 33 | 1/42 (2.4%) | 1 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Hemoglobin decreased | 6/1378 (0.4%) | 9 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 8/1326 (0.6%) | 11 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Thrombotic microangiopathy | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Cardiac disorders | ||||||||||||||
| Arrhythmia | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Arrhythmia supraventricular | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Asystole | 0/1378 (0%) | 0 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Atrial fibrillation | 1/1378 (0.1%) | 2 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Atrial flutter | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Cardiac disorder | 2/1378 (0.1%) | 4 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cardiac pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Conduction disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Myocardial ischemia | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 4 | 2/42 (4.8%) | 2 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Premature ventricular contractions | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Sinus tachycardia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Supraventricular extrasystoles | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Supraventricular tachycardia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ventricular arrhythmia | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ear and labyrinth disorders | ||||||||||||||
| Ear pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Tinnitus | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Eye disorders | ||||||||||||||
| Cataract | 1/1378 (0.1%) | 8 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Conjunctivitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Eyelid function disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Retinal detachment | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Watering eyes | 1/1378 (0.1%) | 1 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 2/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastrointestinal disorders | ||||||||||||||
| Abdominal distension | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Abdominal pain | 31/1378 (2.2%) | 32 | 1/108 (0.9%) | 1 | 2/108 (1.9%) | 2 | 28/1326 (2.1%) | 35 | 1/42 (2.4%) | 1 | 3/44 (6.8%) | 5 | 0/0 (NaN) | 0 |
| Anal pain | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cecal obstruction | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cheilitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colitis | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colonic obstruction | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Colonic stenosis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Constipation | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 9/1326 (0.7%) | 10 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Diarrhea | 107/1378 (7.8%) | 125 | 15/108 (13.9%) | 28 | 13/108 (12%) | 17 | 192/1326 (14.5%) | 250 | 6/42 (14.3%) | 7 | 7/44 (15.9%) | 11 | 0/0 (NaN) | 0 |
| Dry mouth | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Dyspepsia | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Dysphagia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ear, nose and throat examination abnormal | 18/1378 (1.3%) | 20 | 2/108 (1.9%) | 2 | 2/108 (1.9%) | 2 | 63/1326 (4.8%) | 77 | 3/42 (7.1%) | 4 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Enteritis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Esophagitis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastric hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastric ulcer | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastritis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gastrointestinal disorder | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Gastrointestinal pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hemorrhoids | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ileal obstruction | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ileal perforation | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ileus | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 5 | 0/42 (0%) | 0 | 1/44 (2.3%) | 2 | 0/0 (NaN) | 0 |
| Intestinal necrosis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Large intestinal mucositis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Lip pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Lower gastrointestinal hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Mucositis oral | 18/1378 (1.3%) | 19 | 2/108 (1.9%) | 2 | 2/108 (1.9%) | 6 | 44/1326 (3.3%) | 51 | 3/42 (7.1%) | 3 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Nausea | 35/1378 (2.5%) | 41 | 9/108 (8.3%) | 10 | 6/108 (5.6%) | 6 | 56/1326 (4.2%) | 66 | 0/42 (0%) | 0 | 8/44 (18.2%) | 10 | 0/0 (NaN) | 0 |
| Oral pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pancreatitis | 0/1378 (0%) | 0 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Proctitis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Rectal pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Rectal perforation | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Small intestinal obstruction | 5/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vomiting | 40/1378 (2.9%) | 44 | 7/108 (6.5%) | 10 | 5/108 (4.6%) | 5 | 41/1326 (3.1%) | 45 | 0/42 (0%) | 0 | 4/44 (9.1%) | 6 | 0/0 (NaN) | 0 |
| General disorders | ||||||||||||||
| Chest pain | 5/1378 (0.4%) | 6 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 6/1326 (0.5%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Edema limbs | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Fatigue | 53/1378 (3.8%) | 80 | 2/108 (1.9%) | 2 | 9/108 (8.3%) | 11 | 77/1326 (5.8%) | 122 | 1/42 (2.4%) | 1 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Flu-like symptoms | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gait abnormal | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| General symptom | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ill-defined disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pain | 4/1378 (0.3%) | 5 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hepatobiliary disorders | ||||||||||||||
| Gallbladder obstruction | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hepatic failure | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hepatobiliary disease | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Immune system disorders | ||||||||||||||
| Cytokine release syndrome | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hypersensitivity | 28/1378 (2%) | 29 | 0/108 (0%) | 0 | 2/108 (1.9%) | 2 | 62/1326 (4.7%) | 65 | 1/42 (2.4%) | 2 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Infections and infestations | ||||||||||||||
| Abdominal infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Bladder infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Bronchitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Catheter related infection | 5/1378 (0.4%) | 5 | 0/108 (0%) | 0 | 1/108 (0.9%) | 2 | 13/1326 (1%) | 14 | 1/42 (2.4%) | 1 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Colitis, infectious (e.g., Clostridium difficile) | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Device related infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Ileal infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Infection | 5/1378 (0.4%) | 5 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 6/1326 (0.5%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Infectious colitis | 8/1378 (0.6%) | 10 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Joint infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Kidney infection | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Nail infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 5 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Otitis media | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pelvic infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pharyngitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pneumonia | 10/1378 (0.7%) | 10 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Salivary gland infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Sepsis | 4/1378 (0.3%) | 4 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 6/1326 (0.5%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Sinusitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Skin infection | 3/1378 (0.2%) | 4 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 24/1326 (1.8%) | 41 | 1/42 (2.4%) | 1 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Soft tissue infection | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Upper aerodigestive tract infection | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Upper respiratory infection | 3/1378 (0.2%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Urinary tract infection | 4/1378 (0.3%) | 4 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 8/1326 (0.6%) | 8 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Wound infection | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||
| Arterial injury - Extremity-lower | 0/1378 (0%) | 0 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Fracture | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Injury to superior vena cava | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Intestinal stoma site bleeding | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Postoperative hemorrhage | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vascular access complication | 22/1378 (1.6%) | 33 | 3/108 (2.8%) | 3 | 5/108 (4.6%) | 8 | 18/1326 (1.4%) | 34 | 1/42 (2.4%) | 1 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Investigations | ||||||||||||||
| Activated partial thromboplastin time prolonged | 1/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Alanine aminotransferase increased | 16/1378 (1.2%) | 21 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 14/1326 (1.1%) | 18 | 1/42 (2.4%) | 1 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Alkaline phosphatase increased | 2/1378 (0.1%) | 4 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Aspartate aminotransferase increased | 10/1378 (0.7%) | 10 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 11/1326 (0.8%) | 12 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Blood bilirubin increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Coagulopathy | 3/1378 (0.2%) | 7 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 10 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Creatinine increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Gamma-glutamyltransferase increased | 2/1378 (0.1%) | 5 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| INR increased | 16/1378 (1.2%) | 39 | 0/108 (0%) | 0 | 1/108 (0.9%) | 3 | 15/1326 (1.1%) | 30 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Leukocyte count decreased | 25/1378 (1.8%) | 32 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 31/1326 (2.3%) | 36 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Lipase increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Lymphocyte count decreased | 5/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 8/1326 (0.6%) | 14 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Neutrophil count decreased | 131/1378 (9.5%) | 148 | 14/108 (13%) | 18 | 18/108 (16.7%) | 20 | 154/1326 (11.6%) | 175 | 3/42 (7.1%) | 4 | 4/44 (9.1%) | 4 | 0/0 (NaN) | 0 |
| Platelet count decreased | 6/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum cholesterol increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Weight gain | 1/1378 (0.1%) | 1 | 1/108 (0.9%) | 4 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Weight loss | 2/1378 (0.1%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 9/1326 (0.7%) | 18 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||
| Anorexia | 9/1378 (0.7%) | 9 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 28/1326 (2.1%) | 35 | 1/42 (2.4%) | 1 | 2/44 (4.5%) | 3 | 0/0 (NaN) | 0 |
| Blood glucose increased | 42/1378 (3%) | 99 | 8/108 (7.4%) | 37 | 6/108 (5.6%) | 12 | 32/1326 (2.4%) | 69 | 1/42 (2.4%) | 2 | 1/44 (2.3%) | 6 | 0/0 (NaN) | 0 |
| Dehydration | 10/1378 (0.7%) | 10 | 1/108 (0.9%) | 1 | 3/108 (2.8%) | 3 | 39/1326 (2.9%) | 42 | 0/42 (0%) | 0 | 1/44 (2.3%) | 2 | 0/0 (NaN) | 0 |
| Hyperglycemia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hypokalemia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hyponatremia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum albumin decreased | 2/1378 (0.1%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 8/1326 (0.6%) | 11 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum calcium decreased | 6/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 9/1326 (0.7%) | 9 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Serum magnesium decreased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 26/1326 (2%) | 43 | 0/42 (0%) | 0 | 2/44 (4.5%) | 4 | 0/0 (NaN) | 0 |
| Serum magnesium increased | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Serum phosphate decreased | 2/1378 (0.1%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 9/1326 (0.7%) | 13 | 0/42 (0%) | 0 | 1/44 (2.3%) | 2 | 0/0 (NaN) | 0 |
| Serum potassium decreased | 33/1378 (2.4%) | 43 | 2/108 (1.9%) | 3 | 1/108 (0.9%) | 1 | 84/1326 (6.3%) | 120 | 0/42 (0%) | 0 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Serum potassium increased | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum sodium decreased | 4/1378 (0.3%) | 5 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 9/1326 (0.7%) | 12 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Serum triglycerides increased | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 2/1378 (0.1%) | 4 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 6/1326 (0.5%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Back pain | 4/1378 (0.3%) | 5 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Bone pain | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Chest wall pain | 3/1378 (0.2%) | 3 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Muscle weakness | 4/1378 (0.3%) | 4 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Muscle weakness lower limb | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Muscle weakness right-sided | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Musculoskeletal disorder | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Myalgia | 3/1378 (0.2%) | 3 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Neck pain | 1/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Osteoporosis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pain in extremity | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Trismus | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Nervous system disorders | ||||||||||||||
| Acoustic nerve disorder NOS | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ataxia | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 4/1326 (0.3%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Depressed level of consciousness | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Dizziness | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 12/1326 (0.9%) | 14 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Encephalopathy | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Headache | 4/1378 (0.3%) | 8 | 0/108 (0%) | 0 | 2/108 (1.9%) | 3 | 10/1326 (0.8%) | 12 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Intracranial hemorrhage | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ischemia cerebrovascular | 1/1378 (0.1%) | 1 | 1/108 (0.9%) | 1 | 1/108 (0.9%) | 1 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Laryngeal | 7/1378 (0.5%) | 11 | 1/108 (0.9%) | 1 | 3/108 (2.8%) | 7 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Neuralgia | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Neurological disorder NOS | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Paresthesias | 169/1378 (12.3%) | 295 | 0/108 (0%) | 0 | 3/108 (2.8%) | 3 | 121/1326 (9.1%) | 220 | 4/42 (9.5%) | 7 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Peripheral motor neuropathy | 6/1378 (0.4%) | 10 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 10/1326 (0.8%) | 14 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Peripheral sensory neuropathy | 67/1378 (4.9%) | 116 | 2/108 (1.9%) | 2 | 0/108 (0%) | 0 | 67/1326 (5.1%) | 109 | 1/42 (2.4%) | 1 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Seizure | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Speech disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Syncope | 5/1378 (0.4%) | 5 | 1/108 (0.9%) | 1 | 0/108 (0%) | 0 | 8/1326 (0.6%) | 10 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Syncope vasovagal | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Trigeminal nerve disorder | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vagus nerve disorder | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Psychiatric disorders | ||||||||||||||
| Agitation | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Anxiety | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 1/44 (2.3%) | 6 | 0/0 (NaN) | 0 |
| Confusion | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Depression | 2/1378 (0.1%) | 3 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 4/1326 (0.3%) | 7 | 0/42 (0%) | 0 | 1/44 (2.3%) | 2 | 0/0 (NaN) | 0 |
| Insomnia | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 6/1326 (0.5%) | 6 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Renal and urinary disorders | ||||||||||||||
| Kidney pain | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Renal failure | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Ureteric obstruction | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Urinary retention | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Reproductive system and breast disorders | ||||||||||||||
| Irregular menstruation | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Penile pain | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Adult respiratory distress syndrome | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Bronchospasm | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Cough | 8/1378 (0.6%) | 9 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 12/1326 (0.9%) | 18 | 0/42 (0%) | 0 | 2/44 (4.5%) | 3 | 0/0 (NaN) | 0 |
| Dyspnea | 13/1378 (0.9%) | 18 | 2/108 (1.9%) | 2 | 0/108 (0%) | 0 | 28/1326 (2.1%) | 32 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Epistaxis | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hiccups | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hypoxia | 5/1378 (0.4%) | 6 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Nasal congestion | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pharyngeal examination abnormal | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 8/1326 (0.6%) | 9 | 0/42 (0%) | 0 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Pharyngeal mucositis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 5/1326 (0.4%) | 5 | 0/42 (0%) | 0 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Pleuritic pain | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pneumonitis | 8/1378 (0.6%) | 9 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 1/44 (2.3%) | 1 | 0/0 (NaN) | 0 |
| Respiratory disorder | 2/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Voice alteration | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Dry skin | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 11/1326 (0.8%) | 15 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Erythema multiforme | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hand-and-foot syndrome | 16/1378 (1.2%) | 19 | 2/108 (1.9%) | 2 | 0/108 (0%) | 0 | 40/1326 (3%) | 56 | 1/42 (2.4%) | 1 | 2/44 (4.5%) | 2 | 0/0 (NaN) | 0 |
| Nail disorder | 1/1378 (0.1%) | 3 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 24/1326 (1.8%) | 38 | 2/42 (4.8%) | 3 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pain of skin | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Photosensitivity | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Pruritus | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 3/1326 (0.2%) | 3 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Rash acneiform | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 156/1326 (11.8%) | 259 | 7/42 (16.7%) | 11 | 7/44 (15.9%) | 12 | 0/0 (NaN) | 0 |
| Rash desquamating | 2/1378 (0.1%) | 3 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 116/1326 (8.7%) | 194 | 4/42 (9.5%) | 8 | 8/44 (18.2%) | 12 | 0/0 (NaN) | 0 |
| Skin disorder | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Skin ulceration | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 1/42 (2.4%) | 1 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Urticaria | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 2/1326 (0.2%) | 2 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vascular disorders | ||||||||||||||
| Flushing | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 1/108 (0.9%) | 1 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hematoma | 1/1378 (0.1%) | 1 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hemorrhage | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hot flashes | 1/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 4 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hypertension | 7/1378 (0.5%) | 9 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 4/1326 (0.3%) | 7 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Hypotension | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 7/1326 (0.5%) | 7 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Phlebitis | 0/1378 (0%) | 0 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 1/1326 (0.1%) | 1 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Thrombosis | 43/1378 (3.1%) | 74 | 3/108 (2.8%) | 3 | 5/108 (4.6%) | 5 | 49/1326 (3.7%) | 69 | 2/42 (4.8%) | 2 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
| Vascular disorder | 1/1378 (0.1%) | 2 | 0/108 (0%) | 0 | 0/108 (0%) | 0 | 0/1326 (0%) | 0 | 0/42 (0%) | 0 | 0/44 (0%) | 0 | 0/0 (NaN) | 0 |
Limitations/Caveats
Accrual to arms A and D terminated early based on the results of the planned 2nd interim analysis. Sample sizes limit statistical conclusions for data from the irinotecan treated patients as those treatment arms were discontinued early in the study.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Dr. Steven Alberts |
|---|---|
| Organization | North Central Cancer Treatment Group |
| Phone | 507-284-8432 |
| alberts.steven@mayo.edu |
Responsible Party:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00079274
Other Study ID Numbers:
- NCI-2009-00639
- N0147
- U10CA025224
- CDR0000355132
- NCT00170092
First Posted:
Mar 10, 2004
Last Update Posted:
May 13, 2020
Last Verified:
Apr 1, 2020