Vaccine Therapy With Bevacizumab Versus Bevacizumab Alone in Treating Patients With Recurrent Glioblastoma Multiforme That Can Be Removed by Surgery
Sponsor
Alliance for Clinical Trials in Oncology (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01814813
Collaborator
National Cancer Institute (NCI) (NIH), Agenus Inc. (Industry)
90
417
3
0.2
Study Details
Study Description
Brief Summary
This randomized phase II trial studies how well giving vaccine therapy with or without bevacizumab works in treating patients with recurrent glioblastoma multiforme that can be removed by surgery. Vaccines consisting of heat shock protein-peptide complexes made from a person's own tumor tissue may help the body build an effective immune response to kill tumor cells that may remain after surgery. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them. It is not yet known whether giving vaccine therapy is more effective with or without bevacizumab in treating glioblastoma multiforme.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The purpose of this study is to compare the effects of a vaccine with bevacizumab versus bevacizumab alone on a patient's brain tumor. The vaccine is called heat shock protein peptide complex 96 (HSPPC-96). HSPPC-96 is experimental. Specifically, HSPPC-96 is a protein that may work to help the body have a response against remaining brain tumor cells. Bevacizumab has been approved by the Food and Drug administration for treating brain tumors that grow back. In this study, patients will either get HSPPC-96 vaccine at the same time as bevacizumab, HSPPC vaccine first and then bevacizumab if the tumor comes back, or bevacizumab alone. The use of HSPPC-96 and bevacizumab is investigational.
The primary objective of the study is to determine whether there is an overall survival advantage of HSPPC-96 administered with bevacizumab, given concomitantly or at the point of progression, in comparison with bevacizumab alone in patients with surgically resectable recurrent glioblastoma multiforme.
The secondary objectives are:
-
to evaluate the safety and tolerability of HSPPC-96 with bevacizumab
-
to evaluate the progression free survival of HSPPC-96 with bevacizumab, given concomitantly or at the point of progression.
Patients must undergo surgery within 28 days from pre-registration. There must be confirmation of adequacy of tissue for vaccine manufacture, tumor tissue submitted to Agenus, confirmation of ≥ 90% resection by central radiology review and vaccine manufacture of at least six vials. Patients will be randomized to one of three treatment arms. Please see the "Arms" section for more details.
Patients will be monitored approximately 5 years post-surgery.
Study Design
Study Type:
Interventional
Actual Enrollment
:
90 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase II Randomized Trial Comparing the Efficacy of Heat Shock Protein-Peptide Complex-96 (HSPPC-96) (NSC #725085, ALLIANCE IND # 15380) Vaccine Given With Bevacizumab Versus Bevacizumab Alone in the Treatment of Surgically Resectable Recurrent Glioblastoma Multiforme (GBM)
Actual Study Start Date
:
May 1, 2013
Actual Primary Completion Date
:
Apr 3, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1, HSPPC-96 + concomitant bevacizumab HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. |
Biological: HSPPC-96
intradermal infusion
Drug: bevacizumab
intravenous
|
| Experimental: Arm 2, HSPPC-96 with bevacizumab at progression HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days) NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. |
Biological: HSPPC-96
intradermal infusion
Drug: bevacizumab
intravenous
|
| Active Comparator: Arm 3, Bevacizumab Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) |
Drug: bevacizumab
intravenous
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Up to 5 years post-surgery]
The primary endpoint is overall survival (OS), which is defined as the date from study> registration to the date of death, due to any cause.
Secondary Outcome Measures
- Progression Free Survival (PFS) [Up to 5 years post-surgery]
Time to progression free survival: which is defined as the date from study registration to the date of first observation of disease progression or death due to any cause (whichever comes first). Progressive disease is defined as one or more of the following:New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids, increase by > 50% enhancement from the first post-surgical scan, or a subsequent scan with smaller tumor size, and the scan 8 weeks or later on stable or increasing doses of corticosteroids, clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment, for patients receiving bevacizumab therapy, significant increase in T2/FLAIR non-enhancing lesion.
- Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5) [Up to 3 years]
The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. 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
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Pre-registration (Pre-Surgery) Eligibility Criteria
-
Histologic documentation: Prior histologic diagnosis of GBM at first occurrence
-
Stage: First or second recurrence of GBM or gliosarcoma considered to be surgically resectable
-
Prior Treatment:
-
No radiotherapy within 90 days prior to pre-registration
-
No prior treatment with any anti-angiogenic agent targeting the VEGF pathway including but not limited to bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib
-
No prior treatment with HSPPC-96 or other investigational immunotherapy
-
Must have received prior treatment with radiotherapy and temozolomide for histologically confirmed GBM at initial diagnosis
-
No tumor directed therapy for most recent progression
-
No prior Gliadel® wafers
-
No clinically significant cardiovascular disease:
-
Patients with a history of hypertension must be well controlled (<150/90) on a regimen of antihypertensive therapy.
-
History of arterial thrombotic events within the past 6 months, including transient ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus, unstable angina or angina requiring surgical or medial intervention in the past 6 months, or myocardial infarction (MI). Patients with clinically significant peripheral artery disease (i.e., claudication on less than one block), significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) are not eligible.
-
Patients who have had a deep vein thrombosis or pulmonary embolus within the past 6 months are eligible if they are on stable therapeutic anticoagulation
-
No current New York Heart Association classification II, III or IV congestive heart failure
-
No significant bleeding within the past 6 months; no bleeding diathesis or coagulopathy
-
No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within past 12 months
-
No evidence of any systemic autoimmune disease (e.g. Hashimoto's thyroiditis) and/or any history of primary or secondary immunodeficiency, and no immunosuppressant therapy (with the exception of dexamethasone as noted below) for any reason
-
Age ≥ 18 years of age
-
Karnofsky functional status rating ≥70
-
No more than 16 mg dexamethasone (or equivalent) per day
-
Non-pregnant and non-nursing
Registration (Post-Surgery) Eligibility Criteria
-
Pre-registration eligibility criteria continue to be met
-
Histologic documentation: confirmed histological diagnosis of recurrent GBM or gliosarcoma
-
≥ 90% surgical resection of recurrent GBM confirmed by central radiology review by MRI with or without gadolinium per institutional guidelines. A CT scan is allowable in place of MRI only in situations where an MRI is contraindicated (e.g., patient has a heart pacemaker, metallic devices in the eye, brain or spine, severe claustrophobia).
-
≥ 7 grams of resected tumor available for vaccine manufacture as determined by institutional pathologist
-
Availability of ≥ 6 clinical vials of HSPPC-96
-
Required Initial Laboratory Values:
-
Granulocytes ≥1,500/µL
-
Platelet count ≥100,000/µL
-
Total Bilirubin ≤ 2.0 x ULN
-
UPC ratio <1 or Urine protein ≤ 1+
-
Calculated creatinine clearance ≥ 45 ml/min
-
SGOT/SGPT(AST/ALT) ≤ 2.5 x ULN
-
No serious, non-healing wounds or ulcers
-
At least 7 days since any minor surgery such as port placement
-
No major surgical procedures, open biopsy or significant traumatic injury ≤ 28 days prior to registration or anticipation of need for elective or planned major surgical procedure during the study. Core biopsy or other minor surgical procedures ≤7 days prior to registration.
-
No active or recent hemoptysis (≥½ teaspoon of bright red blood per episode) ≤ 30 days prior to registration
-
No new bleeding on D28 (+/-3) MRI (or CT if MRI is contraindicated)
-
No clinical deterioration at the time of registration/randomization
-
If a second surgery is needed for completion of resection, this should be within 30 days from the first surgery
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Anchorage Associates in Radiation Medicine | Anchorage | Alaska | United States | 98508 |
| 2 | Anchorage Radiation Therapy Center | Anchorage | Alaska | United States | 99504 |
| 3 | Alaska Breast Care and Surgery LLC | Anchorage | Alaska | United States | 99508 |
| 4 | Alaska Oncology and Hematology LLC | Anchorage | Alaska | United States | 99508 |
| 5 | Alaska Regional Hospital | Anchorage | Alaska | United States | 99508 |
| 6 | Alaska Women's Cancer Care | Anchorage | Alaska | United States | 99508 |
| 7 | Anchorage Oncology Centre | Anchorage | Alaska | United States | 99508 |
| 8 | Katmai Oncology Group | Anchorage | Alaska | United States | 99508 |
| 9 | Providence Alaska Medical Center | Anchorage | Alaska | United States | 99508 |
| 10 | Mercy Cancer Center-Hot Springs | Hot Springs | Arkansas | United States | 71913 |
| 11 | University of Arkansas for Medical Sciences | Little Rock | Arkansas | United States | 72205 |
| 12 | Kaiser Permanente-Deer Valley Medical Center | Antioch | California | United States | 94531 |
| 13 | Sutter Auburn Faith Hospital | Auburn | California | United States | 95602 |
| 14 | Sutter Cancer Centers Radiation Oncology Services-Auburn | Auburn | California | United States | 95603 |
| 15 | Alta Bates Summit Medical Center-Herrick Campus | Berkeley | California | United States | 94704 |
| 16 | Providence Saint Joseph Medical Center/Disney Family Cancer Center | Burbank | California | United States | 91505 |
| 17 | Mills - Peninsula Hospitals | Burlingame | California | United States | 94010 |
| 18 | Sutter Cancer Centers Radiation Oncology Services-Cameron Park | Cameron Park | California | United States | 95682 |
| 19 | Eden Hospital Medical Center | Castro Valley | California | United States | 94546 |
| 20 | Sutter Davis Hospital | Davis | California | United States | 95616 |
| 21 | Epic Care-Dublin | Dublin | California | United States | 94568 |
| 22 | Bay Area Breast Surgeons Inc | Emeryville | California | United States | 94608 |
| 23 | Epic Care Partners in Cancer Care | Emeryville | California | United States | 94608 |
| 24 | Kaiser Permanente-Fremont | Fremont | California | United States | 94538 |
| 25 | Fresno Cancer Center | Fresno | California | United States | 93720 |
| 26 | Kaiser Permanente | Fresno | California | United States | 93720 |
| 27 | Kaiser Permanente Los Angeles Medical Center | Los Angeles | California | United States | 90027 |
| 28 | Contra Costa Regional Medical Center | Martinez | California | United States | 94553-3156 |
| 29 | Memorial Medical Center | Modesto | California | United States | 95355 |
| 30 | Kaiser Permanente-Modesto | Modesto | California | United States | 95356 |
| 31 | Palo Alto Medical Foundation-Camino Division | Mountain View | California | United States | 94040 |
| 32 | Palo Alto Medical Foundation-Gynecologic Oncology | Mountain View | California | United States | 94040 |
| 33 | Alta Bates Summit Medical Center - Summit Campus | Oakland | California | United States | 94609 |
| 34 | Bay Area Tumor Institute | Oakland | California | United States | 94609 |
| 35 | Kaiser Permanente Oakland-Broadway | Oakland | California | United States | 94611 |
| 36 | Kaiser Permanente-Oakland | Oakland | California | United States | 94611 |
| 37 | Palo Alto Medical Foundation Health Care | Palo Alto | California | United States | 94301 |
| 38 | Stanford Cancer Institute | Palo Alto | California | United States | 94304 |
| 39 | Kaiser Permanente-Rancho Cordova Cancer Center | Rancho Cordova | California | United States | 95670 |
| 40 | Kaiser Permanente-Redwood City | Redwood City | California | United States | 94063 |
| 41 | Kaiser Permanente-Richmond | Richmond | California | United States | 94801 |
| 42 | Rohnert Park Cancer Center | Rohnert Park | California | United States | 94928 |
| 43 | Kaiser Permanente-Roseville | Roseville | California | United States | 95661 |
| 44 | Sutter Cancer Centers Radiation Oncology Services-Roseville | Roseville | California | United States | 95661 |
| 45 | Sutter Roseville Medical Center | Roseville | California | United States | 95661 |
| 46 | The Permanente Medical Group-Roseville Radiation Oncology | Roseville | California | United States | 95678 |
| 47 | Sutter General Hospital | Sacramento | California | United States | 95816 |
| 48 | Kaiser Permanente-South Sacramento | Sacramento | California | United States | 95823 |
| 49 | South Sacramento Cancer Center | Sacramento | California | United States | 95823 |
| 50 | Kaiser Permanente - Sacramento | Sacramento | California | United States | 95825 |
| 51 | California Pacific Medical Center-Pacific Campus | San Francisco | California | United States | 94115 |
| 52 | Kaiser Permanente-San Francisco | San Francisco | California | United States | 94115 |
| 53 | UCSF Medical Center-Mount Zion | San Francisco | California | United States | 94115 |
| 54 | UCSF Medical Center-Parnassus | San Francisco | California | United States | 94143 |
| 55 | Kaiser Permanente-Santa Teresa-San Jose | San Jose | California | United States | 95119 |
| 56 | Kaiser Permanente San Leandro | San Leandro | California | United States | 94577 |
| 57 | Kaiser Permanente-San Rafael | San Rafael | California | United States | 94903 |
| 58 | Kaiser Permanente Medical Center - Santa Clara | Santa Clara | California | United States | 95051 |
| 59 | Palo Alto Medical Foundation-Santa Cruz | Santa Cruz | California | United States | 95065 |
| 60 | Kaiser Permanente-Santa Rosa | Santa Rosa | California | United States | 95403 |
| 61 | Sutter Pacific Medical Foundation | Santa Rosa | California | United States | 95403 |
| 62 | Kaiser Permanente Cancer Treatment Center | South San Francisco | California | United States | 94080 |
| 63 | Kaiser Permanente-South San Francisco | South San Francisco | California | United States | 94080 |
| 64 | Kaiser Permanente-Stockton | Stockton | California | United States | 95210 |
| 65 | Palo Alto Medical Foundation-Sunnyvale | Sunnyvale | California | United States | 94086 |
| 66 | Sutter Cancer Centers Radiation Oncology Services-Vacaville | Vacaville | California | United States | 95687 |
| 67 | Kaiser Permanente Medical Center-Vacaville | Vacaville | California | United States | 95688 |
| 68 | Kaiser Permanente-Vallejo | Vallejo | California | United States | 94589 |
| 69 | Sutter Solano Medical Center/Cancer Center | Vallejo | California | United States | 94589 |
| 70 | Kaiser Permanente-Walnut Creek | Walnut Creek | California | United States | 94596 |
| 71 | Rocky Mountain Cancer Centers-Aurora | Aurora | Colorado | United States | 80012 |
| 72 | The Medical Center of Aurora | Aurora | Colorado | United States | 80012 |
| 73 | Boulder Community Hospital | Boulder | Colorado | United States | 80301 |
| 74 | Rocky Mountain Cancer Centers-Boulder | Boulder | Colorado | United States | 80304 |
| 75 | Penrose-Saint Francis Healthcare | Colorado Springs | Colorado | United States | 80907 |
| 76 | Rocky Mountain Cancer Centers-Penrose | Colorado Springs | Colorado | United States | 80907 |
| 77 | Porter Adventist Hospital | Denver | Colorado | United States | 80210 |
| 78 | Colorado Blood Cancer Institute | Denver | Colorado | United States | 80218 |
| 79 | Presbyterian - Saint Lukes Medical Center - Health One | Denver | Colorado | United States | 80218 |
| 80 | Rocky Mountain Cancer Centers-Midtown | Denver | Colorado | United States | 80218 |
| 81 | SCL Health Saint Joseph Hospital | Denver | Colorado | United States | 80218 |
| 82 | Rocky Mountain Cancer Centers-Rose | Denver | Colorado | United States | 80220 |
| 83 | Rose Medical Center | Denver | Colorado | United States | 80220 |
| 84 | Colorado Cancer Research Program NCORP | Denver | Colorado | United States | 80222 |
| 85 | Mercy Medical Center | Durango | Colorado | United States | 81301 |
| 86 | Southwest Oncology PC | Durango | Colorado | United States | 81301 |
| 87 | Comprehensive Cancer Care and Research Institute of Colorado LLC | Englewood | Colorado | United States | 80113 |
| 88 | Swedish Medical Center | Englewood | Colorado | United States | 80113 |
| 89 | Mountain Blue Cancer Care Center | Golden | Colorado | United States | 80401 |
| 90 | North Colorado Medical Center | Greeley | Colorado | United States | 80631 |
| 91 | Rocky Mountain Cancer Centers-Greenwood Village | Greenwood Village | Colorado | United States | 80111 |
| 92 | Rocky Mountain Cancer Centers-Lakewood | Lakewood | Colorado | United States | 80228 |
| 93 | Saint Anthony Hospital | Lakewood | Colorado | United States | 80228 |
| 94 | Rocky Mountain Cancer Centers-Littleton | Littleton | Colorado | United States | 80120 |
| 95 | Littleton Adventist Hospital | Littleton | Colorado | United States | 80122 |
| 96 | Rocky Mountain Cancer Centers-Sky Ridge | Lone Tree | Colorado | United States | 80124 |
| 97 | Sky Ridge Medical Center | Lone Tree | Colorado | United States | 80124 |
| 98 | Longmont United Hospital | Longmont | Colorado | United States | 80501 |
| 99 | Rocky Mountain Cancer Centers-Longmont | Longmont | Colorado | United States | 80501 |
| 100 | McKee Medical Center | Loveland | Colorado | United States | 80539 |
| 101 | Parker Adventist Hospital | Parker | Colorado | United States | 80138 |
| 102 | Rocky Mountain Cancer Centers-Parker | Parker | Colorado | United States | 80138 |
| 103 | Saint Mary Corwin Medical Center | Pueblo | Colorado | United States | 81004 |
| 104 | Rocky Mountain Cancer Centers - Pueblo | Pueblo | Colorado | United States | 81008 |
| 105 | Rocky Mountain Cancer Centers-Thornton | Thornton | Colorado | United States | 80260 |
| 106 | SCL Health Lutheran Medical Center | Wheat Ridge | Colorado | United States | 80033 |
| 107 | Saint Vincent's Medical Center | Bridgeport | Connecticut | United States | 06606 |
| 108 | Smilow Cancer Hospital Care Center at Saint Francis | Hartford | Connecticut | United States | 06105 |
| 109 | Boca Raton Regional Hospital | Boca Raton | Florida | United States | 33486 |
| 110 | Memorial Regional Hospital/Joe DiMaggio Children's Hospital | Hollywood | Florida | United States | 33021 |
| 111 | Mount Sinai Medical Center | Miami Beach | Florida | United States | 33140 |
| 112 | University of Miami Miller School of Medicine-Sylvester Cancer Center | Miami | Florida | United States | 33136 |
| 113 | Memorial Hospital West | Pembroke Pines | Florida | United States | 33028 |
| 114 | Emory University Hospital Midtown | Atlanta | Georgia | United States | 30308 |
| 115 | Piedmont Hospital | Atlanta | Georgia | United States | 30309 |
| 116 | Emory University/Winship Cancer Institute | Atlanta | Georgia | United States | 30322 |
| 117 | Saint Alphonsus Cancer Care Center-Boise | Boise | Idaho | United States | 83706 |
| 118 | Saint Luke's Mountain States Tumor Institute | Boise | Idaho | United States | 83712 |
| 119 | Kootenai Medical Center | Coeur d'Alene | Idaho | United States | 83814 |
| 120 | Saint Luke's Mountain States Tumor Institute - Fruitland | Fruitland | Idaho | United States | 83619 |
| 121 | Saint Luke's Mountain States Tumor Institute - Meridian | Meridian | Idaho | United States | 83642 |
| 122 | Saint Luke's Mountain States Tumor Institute - Nampa | Nampa | Idaho | United States | 83686 |
| 123 | Kootenai Cancer Center | Post Falls | Idaho | United States | 83854 |
| 124 | Kootenai Cancer Clinic | Sandpoint | Idaho | United States | 83864 |
| 125 | Saint Luke's Mountain States Tumor Institute-Twin Falls | Twin Falls | Idaho | United States | 83301 |
| 126 | Saint Joseph Medical Center | Bloomington | Illinois | United States | 61701 |
| 127 | Illinois CancerCare-Bloomington | Bloomington | Illinois | United States | 61704 |
| 128 | Illinois CancerCare-Canton | Canton | Illinois | United States | 61520 |
| 129 | Memorial Hospital of Carbondale | Carbondale | Illinois | United States | 62902 |
| 130 | Illinois CancerCare-Carthage | Carthage | Illinois | United States | 62321 |
| 131 | Centralia Oncology Clinic | Centralia | Illinois | United States | 62801 |
| 132 | Northwestern University | Chicago | Illinois | United States | 60611 |
| 133 | Rush University Medical Center | Chicago | Illinois | United States | 60612 |
| 134 | University of Chicago Comprehensive Cancer Center | Chicago | Illinois | United States | 60637 |
| 135 | Cancer Care Center of Decatur | Decatur | Illinois | United States | 62526 |
| 136 | Decatur Memorial Hospital | Decatur | Illinois | United States | 62526 |
| 137 | Crossroads Cancer Center | Effingham | Illinois | United States | 62401 |
| 138 | Illinois CancerCare-Eureka | Eureka | Illinois | United States | 61530 |
| 139 | NorthShore University HealthSystem-Evanston Hospital | Evanston | Illinois | United States | 60201 |
| 140 | Illinois CancerCare-Galesburg | Galesburg | Illinois | United States | 61401 |
| 141 | Western Illinois Cancer Treatment Center | Galesburg | Illinois | United States | 61401 |
| 142 | Northwestern Medicine Cancer Center Delnor | Geneva | Illinois | United States | 60134 |
| 143 | NorthShore University HealthSystem-Glenbrook Hospital | Glenview | Illinois | United States | 60026 |
| 144 | NorthShore University HealthSystem-Highland Park Hospital | Highland Park | Illinois | United States | 60035 |
| 145 | Illinois CancerCare-Kewanee Clinic | Kewanee | Illinois | United States | 61443 |
| 146 | Illinois CancerCare-Macomb | Macomb | Illinois | United States | 61455 |
| 147 | Illinois CancerCare-Ottawa Clinic | Ottawa | Illinois | United States | 61350 |
| 148 | Radiation Oncology of Northern Illinois | Ottawa | Illinois | United States | 61350 |
| 149 | Illinois CancerCare-Pekin | Pekin | Illinois | United States | 61554 |
| 150 | OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center | Pekin | Illinois | United States | 61554 |
| 151 | Methodist Medical Center of Illinois | Peoria | Illinois | United States | 61603 |
| 152 | Illinois CancerCare-Peoria | Peoria | Illinois | United States | 61615 |
| 153 | OSF Saint Francis Radiation Oncology at Peoria Cancer Center | Peoria | Illinois | United States | 61615 |
| 154 | OSF Saint Francis Medical Center | Peoria | Illinois | United States | 61637 |
| 155 | Illinois CancerCare-Peru | Peru | Illinois | United States | 61354 |
| 156 | Valley Radiation Oncology | Peru | Illinois | United States | 61354 |
| 157 | Illinois CancerCare-Princeton | Princeton | Illinois | United States | 61356 |
| 158 | Central Illinois Hematology Oncology Center | Springfield | Illinois | United States | 62702 |
| 159 | Southern Illinois University School of Medicine | Springfield | Illinois | United States | 62702 |
| 160 | Springfield Clinic | Springfield | Illinois | United States | 62702 |
| 161 | Memorial Medical Center | Springfield | Illinois | United States | 62781 |
| 162 | Cancer Care Specialists of Illinois-Swansea | Swansea | Illinois | United States | 62226 |
| 163 | Northwestern Medicine Cancer Center Warrenville | Warrenville | Illinois | United States | 60555 |
| 164 | Elkhart Clinic | Elkhart | Indiana | United States | 46514-2098 |
| 165 | Michiana Hematology Oncology PC-Elkhart | Elkhart | Indiana | United States | 46514 |
| 166 | Elkhart General Hospital | Elkhart | Indiana | United States | 46515 |
| 167 | Radiation Oncology Associates PC | Fort Wayne | Indiana | United States | 46804 |
| 168 | Parkview Hospital Randallia | Fort Wayne | Indiana | United States | 46805 |
| 169 | Franciscan Health Indianapolis | Indianapolis | Indiana | United States | 46237 |
| 170 | Community Howard Regional Health | Kokomo | Indiana | United States | 46904 |
| 171 | IU Health La Porte Hospital | La Porte | Indiana | United States | 46350 |
| 172 | Memorial Regional Cancer Center Day Road | Mishawaka | Indiana | United States | 46544 |
| 173 | Michiana Hematology Oncology PC-Mishawaka | Mishawaka | Indiana | United States | 46545 |
| 174 | Saint Joseph Regional Medical Center-Mishawaka | Mishawaka | Indiana | United States | 46545 |
| 175 | Michiana Hematology Oncology PC-Plymouth | Plymouth | Indiana | United States | 46563 |
| 176 | Reid Health | Richmond | Indiana | United States | 47374 |
| 177 | Memorial Hospital of South Bend | South Bend | Indiana | United States | 46601 |
| 178 | Michiana Hematology Oncology PC-South Bend | South Bend | Indiana | United States | 46601 |
| 179 | South Bend Clinic | South Bend | Indiana | United States | 46617 |
| 180 | Northern Indiana Cancer Research Consortium | South Bend | Indiana | United States | 46628 |
| 181 | Michiana Hematology Oncology PC-Westville | Westville | Indiana | United States | 46391 |
| 182 | Medical Oncology and Hematology Associates-West Des Moines | Clive | Iowa | United States | 50325 |
| 183 | Mercy Cancer Center-West Lakes | Clive | Iowa | United States | 50325 |
| 184 | Alegent Health Mercy Hospital | Council Bluffs | Iowa | United States | 51503 |
| 185 | Greater Regional Medical Center | Creston | Iowa | United States | 50801 |
| 186 | Medical Oncology and Hematology Associates-Laurel | Des Moines | Iowa | United States | 50314 |
| 187 | Mercy Medical Center - Des Moines | Des Moines | Iowa | United States | 50314 |
| 188 | Mercy Medical Center-West Lakes | West Des Moines | Iowa | United States | 50266 |
| 189 | Kansas Institute of Medicine Cancer and Blood Center | Lenexa | Kansas | United States | 66219 |
| 190 | Minimally Invasive Surgery Hospital | Lenexa | Kansas | United States | 66219 |
| 191 | Menorah Medical Center | Overland Park | Kansas | United States | 66209 |
| 192 | Saint Luke's South Hospital | Overland Park | Kansas | United States | 66213 |
| 193 | Kansas City NCI Community Oncology Research Program | Prairie Village | Kansas | United States | 66208 |
| 194 | Flaget Memorial Hospital | Bardstown | Kentucky | United States | 40004 |
| 195 | Commonwealth Cancer Center-Corbin | Corbin | Kentucky | United States | 40701 |
| 196 | Saint Joseph Radiation Oncology Resource Center | Lexington | Kentucky | United States | 40504 |
| 197 | Saint Joseph Hospital East | Lexington | Kentucky | United States | 40509 |
| 198 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
| 199 | Jewish Hospital | Louisville | Kentucky | United States | 40202 |
| 200 | Norton Hospital Pavilion and Medical Campus | Louisville | Kentucky | United States | 40202 |
| 201 | Saints Mary and Elizabeth Hospital | Louisville | Kentucky | United States | 40215 |
| 202 | Jewish Hospital Medical Center Northeast | Louisville | Kentucky | United States | 40245 |
| 203 | Jewish Hospital Medical Center South | Shepherdsville | Kentucky | United States | 40165 |
| 204 | Maine Medical Center- Scarborough Campus | Scarborough | Maine | United States | 04074 |
| 205 | University of Maryland/Greenebaum Cancer Center | Baltimore | Maryland | United States | 21201 |
| 206 | Sinai Hospital of Baltimore | Baltimore | Maryland | United States | 21215 |
| 207 | Johns Hopkins University/Sidney Kimmel Cancer Center | Baltimore | Maryland | United States | 21287 |
| 208 | Northwest Hospital Center | Randallstown | Maryland | United States | 21133 |
| 209 | Tufts Medical Center | Boston | Massachusetts | United States | 02111 |
| 210 | Massachusetts General Hospital Cancer Center | Boston | Massachusetts | United States | 02114 |
| 211 | Bixby Medical Center | Adrian | Michigan | United States | 49221 |
| 212 | Hickman Cancer Center | Adrian | Michigan | United States | 49221 |
| 213 | Saint Joseph Mercy Hospital | Ann Arbor | Michigan | United States | 48106-0995 |
| 214 | Michigan Cancer Research Consortium NCORP | Ann Arbor | Michigan | United States | 48106 |
| 215 | Beaumont Hospital-Dearborn | Dearborn | Michigan | United States | 48124 |
| 216 | Saint John Hospital and Medical Center | Detroit | Michigan | United States | 48236 |
| 217 | Hurley Medical Center | Flint | Michigan | United States | 48502 |
| 218 | Genesys Hurley Cancer Institute | Flint | Michigan | United States | 48503 |
| 219 | Allegiance Health | Jackson | Michigan | United States | 49201 |
| 220 | Sparrow Hospital | Lansing | Michigan | United States | 48912 |
| 221 | Saint Mary Mercy Hospital | Livonia | Michigan | United States | 48154 |
| 222 | Marquette General Hematology Oncology | Marquette | Michigan | United States | 49855 |
| 223 | Marquette General Hospital | Marquette | Michigan | United States | 49855 |
| 224 | Mercy Memorial Hospital | Monroe | Michigan | United States | 48162 |
| 225 | Toledo Clinic Cancer Centers-Monroe | Monroe | Michigan | United States | 48162 |
| 226 | Saint Joseph Mercy Oakland | Pontiac | Michigan | United States | 48341 |
| 227 | Saint Mary's of Michigan | Saginaw | Michigan | United States | 48601 |
| 228 | Lakeland Hospital | Saint Joseph | Michigan | United States | 49085 |
| 229 | Marie Yeager Cancer Center | Saint Joseph | Michigan | United States | 49085 |
| 230 | Saint John Macomb-Oakland Hospital | Warren | Michigan | United States | 48093 |
| 231 | Fairview Ridges Hospital | Burnsville | Minnesota | United States | 55337 |
| 232 | Mercy Hospital | Coon Rapids | Minnesota | United States | 55433 |
| 233 | Essentia Health Cancer Center | Duluth | Minnesota | United States | 55805 |
| 234 | Essentia Health Saint Mary's Medical Center | Duluth | Minnesota | United States | 55805 |
| 235 | Miller-Dwan Hospital | Duluth | Minnesota | United States | 55805 |
| 236 | Fairview-Southdale Hospital | Edina | Minnesota | United States | 55435 |
| 237 | Unity Hospital | Fridley | Minnesota | United States | 55432 |
| 238 | Fairview Maple Grove Medical Center | Maple Grove | Minnesota | United States | 55369 |
| 239 | Minnesota Oncology Hematology PA-Maplewood | Maplewood | Minnesota | United States | 55109 |
| 240 | Saint John's Hospital - Healtheast | Maplewood | Minnesota | United States | 55109 |
| 241 | Abbott-Northwestern Hospital | Minneapolis | Minnesota | United States | 55407 |
| 242 | Hennepin County Medical Center | Minneapolis | Minnesota | United States | 55415 |
| 243 | Health Partners Inc | Minneapolis | Minnesota | United States | 55454 |
| 244 | New Ulm Medical Center | New Ulm | Minnesota | United States | 56073 |
| 245 | North Memorial Medical Health Center | Robbinsdale | Minnesota | United States | 55422 |
| 246 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 247 | Metro Minnesota Community Oncology Research Consortium | Saint Louis Park | Minnesota | United States | 55416 |
| 248 | Park Nicollet Clinic - Saint Louis Park | Saint Louis Park | Minnesota | United States | 55416 |
| 249 | Regions Hospital | Saint Paul | Minnesota | United States | 55101 |
| 250 | United Hospital | Saint Paul | Minnesota | United States | 55102 |
| 251 | Saint Francis Regional Medical Center | Shakopee | Minnesota | United States | 55379 |
| 252 | Lakeview Hospital | Stillwater | Minnesota | United States | 55082 |
| 253 | Ridgeview Medical Center | Waconia | Minnesota | United States | 55387 |
| 254 | Rice Memorial Hospital | Willmar | Minnesota | United States | 56201 |
| 255 | Minnesota Oncology Hematology PA-Woodbury | Woodbury | Minnesota | United States | 55125 |
| 256 | Fairview Lakes Medical Center | Wyoming | Minnesota | United States | 55092 |
| 257 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
| 258 | Parkland Health Center-Bonne Terre | Bonne Terre | Missouri | United States | 63628 |
| 259 | Saint Francis Medical Center | Cape Girardeau | Missouri | United States | 63703 |
| 260 | Southeast Cancer Center | Cape Girardeau | Missouri | United States | 63703 |
| 261 | Centerpoint Medical Center LLC | Independence | Missouri | United States | 64057 |
| 262 | Capital Region Medical Center-Goldschmidt Cancer Center | Jefferson City | Missouri | United States | 65109 |
| 263 | Saint Luke's Hospital of Kansas City | Kansas City | Missouri | United States | 64111 |
| 264 | North Kansas City Hospital | Kansas City | Missouri | United States | 64116 |
| 265 | Heartland Hematology and Oncology Associates Incorporated | Kansas City | Missouri | United States | 64118 |
| 266 | Research Medical Center | Kansas City | Missouri | United States | 64132 |
| 267 | Saint Luke's East - Lee's Summit | Lee's Summit | Missouri | United States | 64086 |
| 268 | Liberty Radiation Oncology Center | Liberty | Missouri | United States | 64068 |
| 269 | Heartland Regional Medical Center | Saint Joseph | Missouri | United States | 64506 |
| 270 | Saint Joseph Oncology Inc | Saint Joseph | Missouri | United States | 64507 |
| 271 | Washington University School of Medicine | Saint Louis | Missouri | United States | 63110 |
| 272 | Missouri Baptist Medical Center | Saint Louis | Missouri | United States | 63131 |
| 273 | Sainte Genevieve County Memorial Hospital | Sainte Genevieve | Missouri | United States | 63670 |
| 274 | Missouri Baptist Sullivan Hospital | Sullivan | Missouri | United States | 63080 |
| 275 | Missouri Baptist Outpatient Center-Sunset Hills | Sunset Hills | Missouri | United States | 63127 |
| 276 | Community Hospital of Anaconda | Anaconda | Montana | United States | 59711 |
| 277 | Billings Clinic Cancer Center | Billings | Montana | United States | 59101 |
| 278 | Montana Cancer Consortium NCORP | Billings | Montana | United States | 59101 |
| 279 | Saint Vincent Healthcare | Billings | Montana | United States | 59101 |
| 280 | Frontier Cancer Center and Blood Institute-Billings | Billings | Montana | United States | 59102 |
| 281 | Bozeman Deaconess Hospital | Bozeman | Montana | United States | 59715 |
| 282 | Saint James Community Hospital and Cancer Treatment Center | Butte | Montana | United States | 59701 |
| 283 | Benefis Healthcare- Sletten Cancer Institute | Great Falls | Montana | United States | 59405 |
| 284 | Great Falls Clinic | Great Falls | Montana | United States | 59405 |
| 285 | Saint Peter's Community Hospital | Helena | Montana | United States | 59601 |
| 286 | Kalispell Regional Medical Center | Kalispell | Montana | United States | 59901 |
| 287 | Montana Cancer Specialists | Missoula | Montana | United States | 59802 |
| 288 | Saint Patrick Hospital - Community Hospital | Missoula | Montana | United States | 59802 |
| 289 | Community Medical Hospital | Missoula | Montana | United States | 59804 |
| 290 | CHI Health Saint Francis | Grand Island | Nebraska | United States | 68803 |
| 291 | Heartland Hematology and Oncology | Kearney | Nebraska | United States | 68845 |
| 292 | CHI Health Good Samaritan | Kearney | Nebraska | United States | 68847 |
| 293 | Nebraska Cancer Research Center | Lincoln | Nebraska | United States | 68510 |
| 294 | Saint Elizabeth Regional Medical Center | Lincoln | Nebraska | United States | 68510 |
| 295 | Missouri Valley Cancer Consortium | Omaha | Nebraska | United States | 68106 |
| 296 | Alegent Health Immanuel Medical Center | Omaha | Nebraska | United States | 68122 |
| 297 | Hemotology and Oncology Consultants PC | Omaha | Nebraska | United States | 68122 |
| 298 | Alegent Health Bergan Mercy Medical Center | Omaha | Nebraska | United States | 68124 |
| 299 | Alegent Health Lakeside Hospital | Omaha | Nebraska | United States | 68130 |
| 300 | Creighton University Medical Center | Omaha | Nebraska | United States | 68131 |
| 301 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 302 | Midlands Community Hospital | Papillion | Nebraska | United States | 68046 |
| 303 | Dartmouth Hitchcock Medical Center | Lebanon | New Hampshire | United States | 03756 |
| 304 | Hackensack University Medical Center | Hackensack | New Jersey | United States | 07601 |
| 305 | Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital | New Brunswick | New Jersey | United States | 08903 |
| 306 | Rutgers Cancer Institute of New Jersey | New Brunswick | New Jersey | United States | 08903 |
| 307 | The Valley Hospital-Luckow Pavilion | Paramus | New Jersey | United States | 07652 |
| 308 | Neurosurgeons of New Jersey-Ridgewood | Ridgewood | New Jersey | United States | 07450 |
| 309 | Valley Hospital | Ridgewood | New Jersey | United States | 07450 |
| 310 | Valley Health System-Hematology/Oncology | Westwood | New Jersey | United States | 07675 |
| 311 | Columbia University/Herbert Irving Cancer Center | New York | New York | United States | 10032 |
| 312 | University of Rochester | Rochester | New York | United States | 14642 |
| 313 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
| 314 | Duke University Medical Center | Durham | North Carolina | United States | 27710 |
| 315 | East Carolina University | Greenville | North Carolina | United States | 27858 |
| 316 | Wake Forest University Health Sciences | Winston-Salem | North Carolina | United States | 27157 |
| 317 | Altru Cancer Center | Grand Forks | North Dakota | United States | 58201 |
| 318 | Toledo Clinic Cancer Centers-Bowling Green | Bowling Green | Ohio | United States | 43402 |
| 319 | University of Cincinnati/Barrett Cancer Center | Cincinnati | Ohio | United States | 45219 |
| 320 | Good Samaritan Hospital - Cincinnati | Cincinnati | Ohio | United States | 45220 |
| 321 | Bethesda North Hospital | Cincinnati | Ohio | United States | 45242 |
| 322 | TriHealth Cancer Institute-Westside | Cincinnati | Ohio | United States | 45247 |
| 323 | TriHealth Cancer Institute-Anderson | Cincinnati | Ohio | United States | 45255 |
| 324 | Case Western Reserve University | Cleveland | Ohio | United States | 44106 |
| 325 | Ohio State University Comprehensive Cancer Center | Columbus | Ohio | United States | 43210 |
| 326 | Grandview Hospital | Dayton | Ohio | United States | 45405 |
| 327 | Good Samaritan Hospital - Dayton | Dayton | Ohio | United States | 45406 |
| 328 | Miami Valley Hospital | Dayton | Ohio | United States | 45409 |
| 329 | Samaritan North Health Center | Dayton | Ohio | United States | 45415 |
| 330 | Blanchard Valley Hospital | Findlay | Ohio | United States | 45840 |
| 331 | Atrium Medical Center-Middletown Regional Hospital | Franklin | Ohio | United States | 45005-1066 |
| 332 | Wayne Hospital | Greenville | Ohio | United States | 45331 |
| 333 | Kettering Medical Center | Kettering | Ohio | United States | 45429 |
| 334 | Lima Memorial Hospital | Lima | Ohio | United States | 45804 |
| 335 | Toledo Clinic Cancer Centers-Maumee | Maumee | Ohio | United States | 43537 |
| 336 | Toledo Radiation Oncology at Northwest Ohio Onocolgy Center | Maumee | Ohio | United States | 43537 |
| 337 | Saint Charles Hospital | Oregon | Ohio | United States | 43616 |
| 338 | Toledo Clinic Cancer Centers-Oregon | Oregon | Ohio | United States | 43616 |
| 339 | Flower Hospital | Sylvania | Ohio | United States | 43560 |
| 340 | Mercy Hospital of Tiffin | Tiffin | Ohio | United States | 44883 |
| 341 | The Toledo Hospital/Toledo Children's Hospital | Toledo | Ohio | United States | 43606 |
| 342 | Saint Vincent Mercy Medical Center | Toledo | Ohio | United States | 43608 |
| 343 | University of Toledo | Toledo | Ohio | United States | 43614 |
| 344 | Mercy Saint Anne Hospital | Toledo | Ohio | United States | 43623 |
| 345 | Toledo Clinic Cancer Centers-Toledo | Toledo | Ohio | United States | 43623 |
| 346 | Upper Valley Medical Center | Troy | Ohio | United States | 45373 |
| 347 | Fulton County Health Center | Wauseon | Ohio | United States | 43567 |
| 348 | University Pointe | West Chester | Ohio | United States | 45069 |
| 349 | Greene Memorial Hospital | Xenia | Ohio | United States | 45385 |
| 350 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 351 | Oklahoma Cancer Specialists and Research Institute-Tulsa | Tulsa | Oklahoma | United States | 74146 |
| 352 | Saint Charles Health System | Bend | Oregon | United States | 97701 |
| 353 | Clackamas Radiation Oncology Center | Clackamas | Oregon | United States | 97015 |
| 354 | Providence Oncology and Hematology Care Southeast | Clackamas | Oregon | United States | 97015 |
| 355 | Bay Area Hospital | Coos Bay | Oregon | United States | 97420 |
| 356 | Legacy Mount Hood Medical Center | Gresham | Oregon | United States | 97030 |
| 357 | Providence Milwaukie Hospital | Milwaukie | Oregon | United States | 97222 |
| 358 | Providence Newberg Medical Center | Newberg | Oregon | United States | 97132 |
| 359 | Providence Willamette Falls Medical Center | Oregon City | Oregon | United States | 97045 |
| 360 | Legacy Good Samaritan Hospital and Medical Center | Portland | Oregon | United States | 97210 |
| 361 | Providence Portland Medical Center | Portland | Oregon | United States | 97213 |
| 362 | Providence Saint Vincent Medical Center | Portland | Oregon | United States | 97225 |
| 363 | Legacy Meridian Park Hospital | Tualatin | Oregon | United States | 97062 |
| 364 | Lehigh Valley Hospital-Cedar Crest | Allentown | Pennsylvania | United States | 18103 |
| 365 | Lehigh Valley Hospital - Muhlenberg | Bethlehem | Pennsylvania | United States | 18017 |
| 366 | University of Pittsburgh Cancer Institute (UPCI) | Pittsburgh | Pennsylvania | United States | 15232 |
| 367 | Avera Cancer Institute | Sioux Falls | South Dakota | United States | 57105 |
| 368 | Memorial Hospital | Chattanooga | Tennessee | United States | 37404 |
| 369 | Pulmonary Medicine Center of Chattanooga-Hixson | Hixson | Tennessee | United States | 37343 |
| 370 | Memorial GYN Plus | Ooltewah | Tennessee | United States | 37363 |
| 371 | Saint Joseph Regional Cancer Center | Bryan | Texas | United States | 77802 |
| 372 | Huntsman Cancer Institute/University of Utah | Salt Lake City | Utah | United States | 84112 |
| 373 | Inova Fairfax Hospital | Falls Church | Virginia | United States | 22042 |
| 374 | Fredericksburg Oncology Inc | Fredericksburg | Virginia | United States | 22401 |
| 375 | Sentara Norfolk General Hospital | Norfolk | Virginia | United States | 23507 |
| 376 | Providence Regional Cancer System-Aberdeen | Aberdeen | Washington | United States | 98520 |
| 377 | Cancer Care Center at Island Hospital | Anacortes | Washington | United States | 98221 |
| 378 | Swedish Cancer Institute-Eastside Oncology Hematology | Bellevue | Washington | United States | 98005 |
| 379 | PeaceHealth Saint Joseph Medical Center | Bellingham | Washington | United States | 98225 |
| 380 | Harrison HealthPartners Hematology and Oncology-Bremerton | Bremerton | Washington | United States | 98310 |
| 381 | Harrison Medical Center | Bremerton | Washington | United States | 98310 |
| 382 | Highline Medical Center-Main Campus | Burien | Washington | United States | 98166 |
| 383 | Providence Regional Cancer System-Centralia | Centralia | Washington | United States | 98531 |
| 384 | Swedish Medical Center-Edmonds | Edmonds | Washington | United States | 98026 |
| 385 | Saint Elizabeth Hospital | Enumclaw | Washington | United States | 98022 |
| 386 | Providence Regional Cancer Partnership | Everett | Washington | United States | 98201 |
| 387 | Saint Francis Hospital | Federal Way | Washington | United States | 98003 |
| 388 | Swedish Cancer Institute-Issaquah | Issaquah | Washington | United States | 98029 |
| 389 | Providence Regional Cancer System-Lacey | Lacey | Washington | United States | 98503 |
| 390 | Saint Clare Hospital | Lakewood | Washington | United States | 98499 |
| 391 | PeaceHealth Saint John Medical Center | Longview | Washington | United States | 98632 |
| 392 | Harrison HealthPartners Hematology and Oncology-Poulsbo | Poulsbo | Washington | United States | 98370 |
| 393 | Minor and James Medical PLLC | Seattle | Washington | United States | 98104 |
| 394 | Pacific Gynecology Specialists | Seattle | Washington | United States | 98104 |
| 395 | Swedish Medical Center-Ballard Campus | Seattle | Washington | United States | 98107 |
| 396 | Group Health Cooperative-Seattle | Seattle | Washington | United States | 98112 |
| 397 | Swedish Medical Center-First Hill | Seattle | Washington | United States | 98122-4307 |
| 398 | Providence Regional Cancer System-Shelton | Shelton | Washington | United States | 98584 |
| 399 | Rockwood Clinic Cancer Treatment Center-Valley | Spokane Valley | Washington | United States | 99216 |
| 400 | Rockwood Cancer Treatment Center-DHEC-Downtown | Spokane | Washington | United States | 99204 |
| 401 | Evergreen Hematology and Oncology PS | Spokane | Washington | United States | 99218 |
| 402 | Franciscan Research Center-Northwest Medical Plaza | Tacoma | Washington | United States | 98405 |
| 403 | Northwest Medical Specialties PLLC | Tacoma | Washington | United States | 98405 |
| 404 | PeaceHealth Southwest Medical Center | Vancouver | Washington | United States | 98664 |
| 405 | Compass Oncology Vancouver | Vancouver | Washington | United States | 98684 |
| 406 | Legacy Salmon Creek Hospital | Vancouver | Washington | United States | 98686 |
| 407 | Providence Saint Mary Regional Cancer Center | Walla Walla | Washington | United States | 99362 |
| 408 | North Star Lodge Cancer Center at Yakima Valley Memorial Hospital | Yakima | Washington | United States | 98902 |
| 409 | Providence Regional Cancer System-Yelm | Yelm | Washington | United States | 98597 |
| 410 | University of Wisconsin Hospital and Clinics | Madison | Wisconsin | United States | 53792 |
| 411 | Aurora Saint Luke's Medical Center | Milwaukee | Wisconsin | United States | 53215 |
| 412 | Cancer Center of Western Wisconsin | New Richmond | Wisconsin | United States | 54017 |
| 413 | Aurora Cancer Care-Racine | Racine | Wisconsin | United States | 53406 |
| 414 | Cheyenne Regional Medical Center-West | Cheyenne | Wyoming | United States | 82001 |
| 415 | Big Horn Basin Cancer Center | Cody | Wyoming | United States | 82414 |
| 416 | Billings Clinic-Cody | Cody | Wyoming | United States | 82414 |
| 417 | Welch Cancer Center | Sheridan | Wyoming | United States | 82801 |
Sponsors and Collaborators
- Alliance for Clinical Trials in Oncology
- National Cancer Institute (NCI)
- Agenus Inc.
Investigators
- Study Chair: Ian Parney, MD, PhD, Mayo Clinic
- Study Chair: Orin Bloch, MD, Northwestern University
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01814813
Other Study ID Numbers:
- A071101
- U10CA031946
- NCI-2013-00444
First Posted:
Mar 20, 2013
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab |
|---|---|---|---|
| Arm/Group Description | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. HSPPC-96: intradermal infusion bevacizumab: intravenous | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days)> > NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. HSPPC-96: intradermal infusion. bevacizumab: intravenous | Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) bevacizumab: intravenous |
| Period Title: Overall Study | |||
| STARTED | 29 | 30 | 31 |
| COMPLETED | 29 | 30 | 31 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab | Total |
|---|---|---|---|---|
| Arm/Group Description | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. HSPPC-96: intradermal infusion bevacizumab: intravenous | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days) NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. HSPPC-96: intradermal infusion. bevacizumab: intravenous | Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) bevacizumab: intravenous | Total of all reporting groups |
| Overall Participants | 29 | 30 | 31 | 90 |
| Age, Customized (Count of Participants) | ||||
| <55 |
13
44.8%
|
12
40%
|
14
45.2%
|
39
43.3%
|
| >=55 |
16
55.2%
|
18
60%
|
17
54.8%
|
51
56.7%
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
6
20.7%
|
5
16.7%
|
14
45.2%
|
25
27.8%
|
| Male |
23
79.3%
|
25
83.3%
|
17
54.8%
|
65
72.2%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
3.3%
|
1
3.2%
|
2
2.2%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
3.4%
|
1
3.3%
|
2
6.5%
|
4
4.4%
|
| White |
28
96.6%
|
26
86.7%
|
26
83.9%
|
80
88.9%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
2
6.7%
|
2
6.5%
|
4
4.4%
|
| Karnofsky PS (Count of Participants) | ||||
| 70 |
6
20.7%
|
7
23.3%
|
6
19.4%
|
19
21.1%
|
| 80-100 |
23
79.3%
|
23
76.7%
|
25
80.6%
|
71
78.9%
|
Outcome Measures
| Title | Overall Survival (OS) |
|---|---|
| Description | The primary endpoint is overall survival (OS), which is defined as the date from study> registration to the date of death, due to any cause. |
| Time Frame | Up to 5 years post-surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab |
|---|---|---|---|
| Arm/Group Description | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. HSPPC-96: intradermal infusion bevacizumab: intravenous | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days)> > NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. HSPPC-96: intradermal infusion. bevacizumab: intravenous | Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) bevacizumab: intravenous |
| Measure Participants | 29 | 30 | 31 |
| Median (95% Confidence Interval) [months] |
6.6
|
9.2
|
10.7
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm 1, HSPPC-96 + Concomitant Bevacizumab, Arm 2, HSPPC-96 With Bevacizumab at Progression, Arm 3, Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.16 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Progression Free Survival (PFS) |
|---|---|
| Description | Time to progression free survival: which is defined as the date from study registration to the date of first observation of disease progression or death due to any cause (whichever comes first). Progressive disease is defined as one or more of the following:New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids, increase by > 50% enhancement from the first post-surgical scan, or a subsequent scan with smaller tumor size, and the scan 8 weeks or later on stable or increasing doses of corticosteroids, clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment, for patients receiving bevacizumab therapy, significant increase in T2/FLAIR non-enhancing lesion. |
| Time Frame | Up to 5 years post-surgery |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab |
|---|---|---|---|
| Arm/Group Description | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. HSPPC-96: intradermal infusion bevacizumab: intravenous | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days)> > NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. HSPPC-96: intradermal infusion. bevacizumab: intravenous | Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) bevacizumab: intravenous |
| Measure Participants | 29 | 30 | 31 |
| Median (95% Confidence Interval) [months] |
3.7
|
2.5
|
5.3
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm 1, HSPPC-96 + Concomitant Bevacizumab, Arm 2, HSPPC-96 With Bevacizumab at Progression |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.01 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Title | Toxicity, Assessed Using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 (v5) |
|---|---|
| Description | The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns within patient groups. In addition, we will review all adverse event data that is graded as 3, 4, or 5 and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The overall toxicity rates (percentages) for grade 3 or higher adverse events considered at least possibly related to treatment are reported below. |
| Time Frame | Up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who started at least one cycle of treatment and were assessed for adverse events were included in this analysis. |
| Arm/Group Title | Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab |
|---|---|---|---|
| Arm/Group Description | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. HSPPC-96: intradermal infusion bevacizumab: intravenous | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days)> > NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. HSPPC-96: intradermal infusion. bevacizumab: intravenous | Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) bevacizumab: intravenous |
| Measure Participants | 25 | 28 | 20 |
| Grade 3 |
4
13.8%
|
3
10%
|
5
16.1%
|
| Grade 4/5 |
1
3.4%
|
2
6.7%
|
1
3.2%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Arm 1, HSPPC-96 + Concomitant Bevacizumab, Arm 2, HSPPC-96 With Bevacizumab at Progression, Arm 3, Bevacizumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.56 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
Adverse Events
| Time Frame | Adverse events were collected at the end of each cycle for patients randomized to the treatment arm; Up to 5 years. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Each CTCAE term is a representation of a specific event used for medical documentation & analysis & is a single MedDRA Lowest Level Term (LLT). All graded AEs are reported for patients who completed at least 1 cycle of tx & AEs were assessed. Serious AE (SAE) reports may include any secondary serious or non-serious events considered related to the primary event (the reason for filing an expedited report); collectively, these events are referred to as Expedited AEs, & appear in the SAE table. | |||||
| Arm/Group Title | Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab | |||
| Arm/Group Description | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles), plus bevacizumab 10 mg/kg intravenous (IV) on day 1 of each cycle, until progression. HSPPC-96 should be administered at least 60 minutes prior to starting bevacizumab infusion. (1 cycle=14 days) Note: If HSPPC-96 treatment has ended but there is no evidence of disease progression, the patient should continue to receive bevacizumab at the specified dose until progression. HSPPC-96: intradermal infusion bevacizumab: intravenous | HSPPC-96 0.4mL intradermal on days 1 and 8 of cycles 1 and 2, then on day 1 of each cycle, up to a maximum of 12 doses (10 cycles). At progression: bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until further progression. (1 cycle = 14 days) NOTE: It is possible that HSPPC-96 vaccination may end prior to evidence of progression. In this instance it is important to wait until there is confirmed evidence of progression before initiating treatment with bevacizumab. Upon confirmation of progression the patient should initiate bevacizumab within 7-42 days from the last dose of vaccine. HSPPC-96: intradermal infusion. bevacizumab: intravenous | Bevacizumab 10mg/kg intravenous (IV) on day 1 of each cycle, until progression. (1 cycle = 14 days) bevacizumab: intravenous | |||
All Cause Mortality |
||||||
| Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/25 (0%) | 2/28 (7.1%) | 1/20 (5%) | |||
Serious Adverse Events |
||||||
| Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/25 (24%) | 10/28 (35.7%) | 4/20 (20%) | |||
| Cardiac disorders | ||||||
| Sinus tachycardia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Gastrointestinal disorders | ||||||
| Gastrointestinal disorders - Other, specify | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Intra-abdominal hemorrhage | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Vomiting | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/20 (0%) | 0 |
| General disorders | ||||||
| Death NOS | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Infections and infestations | ||||||
| Infections and infestations - Other, specify | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Meningitis | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Sepsis | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Soft tissue infection | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Wound dehiscence | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Metabolism and nutrition disorders | ||||||
| Dehydration | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/20 (0%) | 0 |
| Hypernatremia | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 0/20 (0%) | 0 |
| Hyponatremia | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Generalized muscle weakness | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Nervous system disorders | ||||||
| Encephalopathy | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Headache | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Hydrocephalus | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Intracranial hemorrhage | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| Lethargy | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Nervous system disorders - Other, specify | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Paresthesia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Seizure | 1/25 (4%) | 1 | 2/28 (7.1%) | 3 | 2/20 (10%) | 2 |
| Somnolence | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Tremor | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Psychiatric disorders | ||||||
| Agitation | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Confusion | 0/25 (0%) | 0 | 3/28 (10.7%) | 3 | 0/20 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Atelectasis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Hypoxia | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| Vascular disorders | ||||||
| Hematoma | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Thromboembolic event | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
| Arm 1, HSPPC-96 + Concomitant Bevacizumab | Arm 2, HSPPC-96 With Bevacizumab at Progression | Arm 3, Bevacizumab | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 20/25 (80%) | 23/28 (82.1%) | 18/20 (90%) | |||
| Blood and lymphatic system disorders | ||||||
| Anemia | 4/25 (16%) | 4 | 2/28 (7.1%) | 6 | 1/20 (5%) | 1 |
| Cardiac disorders | ||||||
| Palpitations | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 3 |
| Supraventricular tachycardia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Ear and labyrinth disorders | ||||||
| Ear and labyrinth disorders - Other, specify | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 0/20 (0%) | 0 |
| Tinnitus | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 4 |
| Vertigo | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 3 |
| Eye disorders | ||||||
| Blurred vision | 2/25 (8%) | 9 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Eye disorders - Other, specify | 1/25 (4%) | 1 | 1/28 (3.6%) | 8 | 0/20 (0%) | 0 |
| Optic nerve disorder | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 3 |
| Photophobia | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Gastrointestinal disorders | ||||||
| Abdominal pain | 2/25 (8%) | 2 | 1/28 (3.6%) | 7 | 0/20 (0%) | 0 |
| Anal hemorrhage | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Bloating | 0/25 (0%) | 0 | 1/28 (3.6%) | 9 | 0/20 (0%) | 0 |
| Constipation | 2/25 (8%) | 6 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Diarrhea | 1/25 (4%) | 2 | 1/28 (3.6%) | 14 | 4/20 (20%) | 21 |
| Dysphagia | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Fecal incontinence | 0/25 (0%) | 0 | 1/28 (3.6%) | 4 | 0/20 (0%) | 0 |
| Flatulence | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 0/20 (0%) | 0 |
| Gastroesophageal reflux disease | 1/25 (4%) | 4 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Hemorrhoidal hemorrhage | 1/25 (4%) | 3 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Hemorrhoids | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Mucositis oral | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| Nausea | 2/25 (8%) | 6 | 1/28 (3.6%) | 2 | 4/20 (20%) | 5 |
| Vomiting | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/20 (0%) | 0 |
| General disorders | ||||||
| Chills | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Edema face | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Edema limbs | 2/25 (8%) | 6 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Fatigue | 8/25 (32%) | 35 | 8/28 (28.6%) | 27 | 6/20 (30%) | 40 |
| Fever | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Flu like symptoms | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Gait disturbance | 0/25 (0%) | 0 | 2/28 (7.1%) | 8 | 0/20 (0%) | 0 |
| Infusion related reaction | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| Injection site reaction | 0/25 (0%) | 0 | 4/28 (14.3%) | 4 | 0/20 (0%) | 0 |
| Non-cardiac chest pain | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Pain | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Immune system disorders | ||||||
| Allergic reaction | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Infections and infestations | ||||||
| Gum infection | 1/25 (4%) | 3 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Infections and infestations - Other, specify | 0/25 (0%) | 0 | 1/28 (3.6%) | 5 | 1/20 (5%) | 1 |
| Otitis media | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Skin infection | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 0/20 (0%) | 0 |
| Wound infection | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Bruising | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Fall | 1/25 (4%) | 2 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Fracture | 0/25 (0%) | 0 | 1/28 (3.6%) | 3 | 1/20 (5%) | 1 |
| Wound complication | 0/25 (0%) | 0 | 1/28 (3.6%) | 7 | 0/20 (0%) | 0 |
| Wound dehiscence | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Investigations | ||||||
| Alanine aminotransferase increased | 1/25 (4%) | 1 | 1/28 (3.6%) | 13 | 1/20 (5%) | 1 |
| Aspartate aminotransferase increased | 0/25 (0%) | 0 | 1/28 (3.6%) | 6 | 1/20 (5%) | 1 |
| Blood bilirubin increased | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 2 |
| Cholesterol high | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 3 |
| Creatinine increased | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 2/20 (10%) | 14 |
| Lymphocyte count decreased | 6/25 (24%) | 16 | 2/28 (7.1%) | 3 | 1/20 (5%) | 1 |
| Neutrophil count decreased | 1/25 (4%) | 1 | 1/28 (3.6%) | 6 | 1/20 (5%) | 1 |
| Platelet count decreased | 3/25 (12%) | 3 | 4/28 (14.3%) | 8 | 0/20 (0%) | 0 |
| Weight gain | 0/25 (0%) | 0 | 1/28 (3.6%) | 7 | 1/20 (5%) | 1 |
| Weight loss | 2/25 (8%) | 5 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| White blood cell decreased | 3/25 (12%) | 5 | 2/28 (7.1%) | 6 | 2/20 (10%) | 6 |
| Metabolism and nutrition disorders | ||||||
| Anorexia | 3/25 (12%) | 8 | 3/28 (10.7%) | 4 | 1/20 (5%) | 4 |
| Dehydration | 2/25 (8%) | 5 | 2/28 (7.1%) | 6 | 1/20 (5%) | 2 |
| Hyperglycemia | 1/25 (4%) | 2 | 4/28 (14.3%) | 17 | 2/20 (10%) | 7 |
| Hyperkalemia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 2/20 (10%) | 4 |
| Hypernatremia | 0/25 (0%) | 0 | 1/28 (3.6%) | 4 | 0/20 (0%) | 0 |
| Hypertriglyceridemia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 5 |
| Hyperuricemia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 4 |
| Hypoalbuminemia | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 2/20 (10%) | 2 |
| Hypocalcemia | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| Hypokalemia | 1/25 (4%) | 1 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Hypomagnesemia | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Hyponatremia | 0/25 (0%) | 0 | 2/28 (7.1%) | 15 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 2/25 (8%) | 14 | 2/28 (7.1%) | 13 | 1/20 (5%) | 6 |
| Generalized muscle weakness | 1/25 (4%) | 2 | 2/28 (7.1%) | 2 | 0/20 (0%) | 0 |
| Joint range of motion decreased | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Muscle weakness left-sided | 1/25 (4%) | 2 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Muscle weakness lower limb | 1/25 (4%) | 2 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Muscle weakness right-sided | 2/25 (8%) | 7 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Musculoskeletal and connective tissue disorder - Other, specify | 2/25 (8%) | 2 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Neck pain | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 1/20 (5%) | 3 |
| Pain in extremity | 1/25 (4%) | 5 | 1/28 (3.6%) | 1 | 2/20 (10%) | 4 |
| Nervous system disorders | ||||||
| Amnesia | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Cognitive disturbance | 0/25 (0%) | 0 | 1/28 (3.6%) | 8 | 0/20 (0%) | 0 |
| Concentration impairment | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Dizziness | 0/25 (0%) | 0 | 1/28 (3.6%) | 9 | 0/20 (0%) | 0 |
| Dysarthria | 0/25 (0%) | 0 | 2/28 (7.1%) | 2 | 0/20 (0%) | 0 |
| Dysgeusia | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Dysphasia | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Encephalopathy | 0/25 (0%) | 0 | 1/28 (3.6%) | 11 | 0/20 (0%) | 0 |
| Headache | 6/25 (24%) | 13 | 4/28 (14.3%) | 11 | 5/20 (25%) | 7 |
| Ischemia cerebrovascular | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 0/20 (0%) | 0 |
| Memory impairment | 2/25 (8%) | 7 | 4/28 (14.3%) | 9 | 0/20 (0%) | 0 |
| Nervous system disorders - Other, specify | 2/25 (8%) | 11 | 2/28 (7.1%) | 8 | 0/20 (0%) | 0 |
| Peripheral sensory neuropathy | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 2 |
| Presyncope | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Seizure | 3/25 (12%) | 3 | 3/28 (10.7%) | 8 | 1/20 (5%) | 1 |
| Syncope | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Psychiatric disorders | ||||||
| Anxiety | 1/25 (4%) | 1 | 2/28 (7.1%) | 2 | 1/20 (5%) | 3 |
| Confusion | 0/25 (0%) | 0 | 2/28 (7.1%) | 15 | 0/20 (0%) | 0 |
| Depression | 2/25 (8%) | 6 | 1/28 (3.6%) | 3 | 0/20 (0%) | 0 |
| Insomnia | 0/25 (0%) | 0 | 3/28 (10.7%) | 10 | 0/20 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Proteinuria | 1/25 (4%) | 2 | 2/28 (7.1%) | 8 | 8/20 (40%) | 38 |
| Urinary frequency | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 0/20 (0%) | 0 |
| Urinary incontinence | 0/25 (0%) | 0 | 1/28 (3.6%) | 6 | 0/20 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Irregular menstruation | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 2 |
| Prostatic obstruction | 1/25 (4%) | 2 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Allergic rhinitis | 0/25 (0%) | 0 | 1/28 (3.6%) | 5 | 1/20 (5%) | 12 |
| Cough | 1/25 (4%) | 3 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Epistaxis | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 2/20 (10%) | 4 |
| Hoarseness | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 1/20 (5%) | 1 |
| Nasal congestion | 0/25 (0%) | 0 | 1/28 (3.6%) | 2 | 0/20 (0%) | 0 |
| Postnasal drip | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 10 |
| Sore throat | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||
| Pruritus | 0/25 (0%) | 0 | 1/28 (3.6%) | 1 | 1/20 (5%) | 1 |
| Rash acneiform | 1/25 (4%) | 2 | 1/28 (3.6%) | 3 | 0/20 (0%) | 0 |
| Rash maculo-papular | 2/25 (8%) | 2 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Skin and subcutaneous tissue disorders - Other, specify | 1/25 (4%) | 3 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Skin hyperpigmentation | 0/25 (0%) | 0 | 0/28 (0%) | 0 | 1/20 (5%) | 1 |
| Social circumstances | ||||||
| Social circumstances - Other, specify | 1/25 (4%) | 2 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Vascular disorders | ||||||
| Hypertension | 13/25 (52%) | 85 | 12/28 (42.9%) | 50 | 13/20 (65%) | 75 |
| Hypotension | 1/25 (4%) | 1 | 0/28 (0%) | 0 | 0/20 (0%) | 0 |
| Thromboembolic event | 4/25 (16%) | 8 | 3/28 (10.7%) | 5 | 1/20 (5%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Ian Parney, MD, PhD |
|---|---|
| Organization | Mayo Clinic |
| Phone | 507-284-8167 |
| Parney.Ian@mayo.edu |
Responsible Party:
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT01814813
Other Study ID Numbers:
- A071101
- U10CA031946
- NCI-2013-00444
First Posted:
Mar 20, 2013
Last Update Posted:
Aug 18, 2021
Last Verified:
Aug 1, 2021