S1406 Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer

• Sponsor: Southwest Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT02164916
• Collaborator: National Cancer Institute (NCI) (NIH), Roche-Genentech (Industry)
• Enrollment: 106
• Locations: 763
• Arms: 2
• Duration (Months): 72.6
• Patients Per Site: 0.1
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This randomized phase II trial studies how well irinotecan hydrochloride and cetuximab with or without vemurafenib works in treating patients with colorectal cancer that has spread to nearby tissue or lymph nodes, that has spread to other places in the body, or cannot be removed by surgery. Irinotecan hydrochloride and vemurafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as cetuximab, may block the ability of tumor cells to grow and spread. It is not yet known whether irinotecan hydrochloride and cetuximab are more effective with or without vemurafenib in treating colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Biological: cetuximab; Drug: irinotecan hydrochloride; Drug: vemurafenib	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To evaluate the progression-free survival (PFS) of v-raf murine sarcoma viral oncogene homolog B (BRAF) mutant metastatic colorectal cancer patients treated with irinotecan (irinotecan hydrochloride), cetuximab, and vemurafenib, compared to a control arm of irinotecan and cetuximab.

SECONDARY OBJECTIVES:

1. To evaluate the frequency and severity of toxicity associated with each of the treatment arms in this patient population.

TERTIARY OBJECTIVES:

1. To evaluate overall survival (OS) in treatment Arms 1 and 2. II. To evaluate the overall response rate (ORR), including confirmed and unconfirmed, complete and partial response, in treatment Arms 1 and 2 in the subset of patients with measurable disease.

2. To estimate rates of OS, ORR, and PFS in patients who register to Arm 3 after disease progression on Arm 1.

3. To evaluate low-frequency Kirsten rat sarcoma viral oncogene homolog (KRAS) or neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutations as detected by high-depth sequencing as predictive biomarkers of efficacy.

4. To evaluate phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) pathway activation through PIK3CA mutations or phosphatase and tensin homolog (PTEN) protein loss as a predictive biomarker of innate resistance to this regimen.

5. To evaluate gene expression signatures from screened patients with v-raf murine sarcoma viral oncogene homolog B wild type (BRAFWT) and BRAFV600E tumors.

6. To provide validation of BRAF immunohistochemistry (IHC) using complementary sequencing methodology from screened patients with BRAFWT and BRAFV600E tumors.

7. To confirm the estimated sensitivity of detectable BRAF V600E circulating cell-free deoxyribonucleic acid (DNA) as a non-invasive biomarker for BRAF V600E mutation as detected by IHC in the primary tumor.

8. To correlate radiographic tumor response with change in quantification of BRAFV600E alleles in circulating cell-free DNA.

9. To monitor for known mechanism of acquired resistance to epidermal growth factor receptor (EGFR) inhibition in circulating cell-free DNA (KRAS, NRAS mutations).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cetuximab intravenously (IV) and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II.

ARM II: Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib orally (PO) twice daily (BID) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2-6 months for 3 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 106 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Phase II Study of Irinotecan and Cetuximab With or Without Vemurafenib in BRAF Mutant Metastatic Colorectal Cancer
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Nov 13, 2017
• Actual Study Completion Date: Nov 19, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (cetuximab, irinotecan hydrochloride) Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II.	Biological: cetuximab; Given IV; Other Names: 11460 205923-56-4 3610 714692 Anti-EGFR Monoclonal Antibody Anti-Epidermal Growth Factor Receptor Monoclonal Antibody C225 C225 monoclonal antibody Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 Immunoglobulin G1 anti-(human epidermal growth factor receptor) (human-mouse monoclonal C225 gamma1-chain) disulfide with human-mouse monoclonal C225 kappa-chain dimer MOAB C225 monoclonal antibody C225 ; Drug: irinotecan hydrochloride; Given IV; Other Names: Campto Camptosar camptothecin-11 CPT-11 irinotecan irinotecan HCl U-101440E
Experimental: Arm II (cetuximab, irinotecan hydrochloride, vemurafenib) Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: cetuximab; Given IV; Other Names: 11460 205923-56-4 3610 714692 Anti-EGFR Monoclonal Antibody Anti-Epidermal Growth Factor Receptor Monoclonal Antibody C225 C225 monoclonal antibody Chimeric Anti-EGFR Monoclonal Antibody Chimeric MoAb C225 Chimeric Monoclonal Antibody C225 Erbitux IMC-C225 Immunoglobulin G1 anti-(human epidermal growth factor receptor) (human-mouse monoclonal C225 gamma1-chain) disulfide with human-mouse monoclonal C225 kappa-chain dimer MOAB C225 monoclonal antibody C225 ; Drug: irinotecan hydrochloride; Given IV; Other Names: Campto Camptosar camptothecin-11 CPT-11 irinotecan irinotecan HCl U-101440E ; Drug: vemurafenib; Given PO; Other Names: BRAF(V600E) kinase inhibitor RO5185426 PLX4032 RG7204 RO5185426 Zelboraf

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [Up to 3 years from randomization]

   From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

Secondary Outcome Measures

1. Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug [Up to 3 years]

   Only adverse events that are possibly, probably or definitely related to study drug are reported.

Other Outcome Measures

1. Overall Survival [Up to 3 years from randomization]

   From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

2. Overall Response Rate [Up to 3 years from randomization]

   Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

3. Progression-free Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 [Up to 3 years from randomization]

   From date of Step 3 Crossover registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.

4. Overall Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 [Up to 3 years from randomization]

   From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.

5. Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1 [Up to 3 years from randomization]

   Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• STEP I INITIAL REGISTRATION: BRAFV600E TESTING:

• Patients must have histologically or cytologically documented adenocarcinoma of the colon or rectum that is either metastatic, or locally advanced and unresectable

• Patients must have BRAFV600E mutant status documented by a Clinical Laboratory Improvements Amendments (CLIA) certified laboratory on a pathology report prior to Step 2 registration; use of an Food and Drug Administration (FDA)-approved test is preferred although other BRAF tests at a CLIA-certified laboratory may also be accepted; if a BRAFV600E mutation is known, then the patient must be registered to Step 2 Randomization immediately following Step 1 Initial Registration; if testing has not been performed locally, BRAFV600E testing must be completed by the central lab prior to Step 2 Randomization; if the specimen does not have a BRAFV600E mutation, the patient is ineligible for Step 2 Randomization

• Brain metastases are allowed if they have been adequately treated with radiotherapy or surgery and stable for at least 90 days prior to Step 1 Initial Registration; eligible patients should be neurologically asymptomatic and without corticosteroid treatment for at least 7 days prior to Step 1 Initial Registration

• Patients must have had one or two prior regimens of systemic chemotherapy for metastatic disease; prior treatment with irinotecan is allowed; a maintenance regimen of 5-fluorouracil or capecitabine, with or without bevacizumab, should not be counted as a separate line of treatment; prior treatment for metastatic disease is not required for patients who experienced disease recurrence during or within 6 months of completion of adjuvant chemotherapy

• Patients must not have been treated with any of the following prior to Step 2

Randomization:

• Cetuximab, panitumumab, or any other monoclonal antibody against EGFR or inhibitor of EGFR

• BRAF inhibitor including, but not limited to, vemurafenib or dabrafenib; regorafenib is not considered a BRAF inhibitor for the purpose of determining trial eligibility

• Mitogen-activated protein/extracellular signal-regulated kinase (MEK) inhibitor including, but not limited to, trametinib or selumetinib

• Previous chemotherapy, immunotherapy, or radiation therapy must have been completed at least 14 days prior to Step 1 Initial Registration and all toxicity must be resolved to Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0) grade 1 (with the exception of CTCAE v4.0 grade 2 neuropathy) prior to Step 1 Initial Registration

• Patients must not have a tumor with a mutation detected in codons 12 or 13 in KRAS; patients must not have a tumor with a known mutation detected in codons 61, 117, or 146 of KRAS or NRAS

• SPECIMEN SUBMISSION CRITERIA:

• Patients must have tumor (slides or block) available for submission for V600E BRAF testing

• Patients must have additional tumor available and be willing to submit tissue and blood samples

• SPECIMEN SUBMISSION CRITERIA REGULATORY CRITERIA:

• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; for Step 1 Initial Registration of patients who have not yet submitted specimens for the central BRAFV600E testing, the appropriate consent form is the Step 1 Consent Form; for both Step 1 Initial Registration and Step 2 Randomization of patients whose BRAF mutation status is already known, the appropriate consent form is the Step 2 Consent Form

• STEP 2 RANDOMIZATION:

• Patients must have BRAFV600E mutation

• Patients must have measurable or non-measurable metastatic disease; computed tomography (CT) scans or magnetic resonance imaging (MRIs) used to assess all disease must have been completed within 28 days prior to Step 2 Randomization; CT scans or MRIs must be assessed and documented on the Baseline Tumor Assessment Form (Response Evaluation Criteria in Solid Tumors [RECIST] 1.1)

• Patients must have a Zubrod performance status of 0-1

• Absolute neutrophil count (ANC) >= 1,500/mcL

• Platelets >= 100,00/mcL

• Hemoglobin >= 9 g/dL

• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x institutional upper limit of normal (IULN) or =< 5 x IULN if liver metastases are present

• Total bilirubin =< 1.5 x IULN

• Serum creatinine =< 1.5 x IULN within 14 days prior to Step 2 Randomization OR

• Calculated creatinine clearance > 60 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to Step 2 Randomization

• Patients must have an electrocardiogram (ECG) within 14 days prior to Step 2 Randomization

• Patients must have corrected QT (QTc) =< 500 msec

• Patients must not have a known history of Gilbert's Syndrome or known homozygosity for the UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1)*28 allele

• Patients must not have interstitial pneumonia or extensive symptomatic interstitial fibrosis of the lung

• Patients must not have an uncontrolled intercurrent illness including, but not limited to, active bleeding diathesis, uncontrolled infection/disorders, nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with the study therapy, or psychiatric illness/social situations which would limit compliance with study requirements

• Patients must be able to swallow pill/tablet and have no refractory nausea, vomiting, malabsorption, external biliary shunt, or significant small bowel resection that would preclude adequate absorption

• Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method while on study and for 30 days after study treatment; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures, he/she is responsible for beginning contraceptive measures

• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years

• STEP 2 RANDOMIZATION REGULATORY CRITERIA:

• Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines; for all patients, the appropriate consent form for this registration is the Step 2 Consent Form

• As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

• STEP 3 CROSSOVER REGISTRATION:

• Patients must have documented disease progression while on Arm 1 of this protocol; the follow-up tumor assessment form documenting disease progression must be submitted to Southwestern Oncology Group (SWOG) prior to Step 3

• Registration to Step 3 Crossover must be within 28 days of discontinuation of Arm 1 protocol treatment; patients going off treatment for any other reason are not eligible

• ANC >= 1,500/mcL within 14 days prior to Step 3 registration

• Platelets >= 100,00/mcL within 14 days prior to Step 3 registration

• Hemoglobin >= 9 g/dL within 14 days prior to Step 3 registration

• AST and ALT =< 2.5 x institutional upper limit of normal (IULN) or =< 5 x IULN if liver metastases are present within 14 days prior to Step 3 registration

• Total bilirubin =< 1.5 x IULN within 14 days prior to Step 3 registration

• Serum creatinine =< 1.5 x IULN within 14 days prior to Step 3 registration OR

• Calculated creatinine clearance > 60 ml/min; the serum creatinine value used in the calculation must have been obtained within 14 days prior to Step 3 registration

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Anchorage Radiation Therapy Center	Anchorage	Alaska	United States	99504
2	Alaska Breast Care and Surgery LLC	Anchorage	Alaska	United States	99508
3	Alaska Oncology and Hematology LLC	Anchorage	Alaska	United States	99508
4	Alaska Regional Hospital	Anchorage	Alaska	United States	99508
5	Alaska Women's Cancer Care	Anchorage	Alaska	United States	99508
6	Anchorage Oncology Centre	Anchorage	Alaska	United States	99508
7	Katmai Oncology Group	Anchorage	Alaska	United States	99508
8	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
9	Fairbanks Memorial Hospital	Fairbanks	Alaska	United States	99701
10	University of Arizona Cancer Center-Orange Grove Campus	Tucson	Arizona	United States	85704
11	University of Arizona Cancer Center-North Campus	Tucson	Arizona	United States	85719
12	The University of Arizona Medical Center-University Campus	Tucson	Arizona	United States	85724
13	Mercy Cancer Center-Hot Springs	Hot Springs	Arkansas	United States	71913
14	Fowler Family Center for Cancer Care	Jonesboro	Arkansas	United States	72401
15	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
16	Veteran's Administration Medical Center	Little Rock	Arkansas	United States	72205
17	Kaiser Permanente-Anaheim	Anaheim	California	United States	92807
18	Kaiser Permanente-Deer Valley Medical Center	Antioch	California	United States	94531
19	Sutter Auburn Faith Hospital	Auburn	California	United States	95602
20	Sutter Cancer Centers Radiation Oncology Services-Auburn	Auburn	California	United States	95603
21	Kaiser Permanente-Baldwin Park	Baldwin Park	California	United States	91706
22	Kaiser Permanente-Bellflower	Bellflower	California	United States	90706
23	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
24	Providence Saint Joseph Medical Center/Disney Family Cancer Center	Burbank	California	United States	91505
25	Mills - Peninsula Hospitals	Burlingame	California	United States	94010
26	Sutter Cancer Centers Radiation Oncology Services-Cameron Park	Cameron Park	California	United States	95682
27	Eden Hospital Medical Center	Castro Valley	California	United States	94546
28	Sutter Davis Hospital	Davis	California	United States	95616
29	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010
30	Epic Care-Dublin	Dublin	California	United States	94568
31	Bay Area Breast Surgeons Inc	Emeryville	California	United States	94608
32	Epic Care Partners in Cancer Care	Emeryville	California	United States	94608
33	Kaiser Permanente Hospital	Fontana	California	United States	92335
34	Kaiser Permanente-Fremont	Fremont	California	United States	94538
35	Kaiser Permanente	Fresno	California	United States	93720
36	Marin Cancer Care Inc	Greenbrae	California	United States	94904
37	Marin General Hospital	Greenbrae	California	United States	94904
38	Kaiser Permanente - Harbor City	Harbor City	California	United States	90710
39	Kaiser Permanente-Irvine	Irvine	California	United States	92618
40	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
41	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
42	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
43	Kaiser Permanente-Cadillac	Los Angeles	California	United States	90034
44	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
45	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
46	Memorial Medical Center	Modesto	California	United States	95355
47	Kaiser Permanente-Modesto	Modesto	California	United States	95356
48	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
49	Palo Alto Medical Foundation-Gynecologic Oncology	Mountain View	California	United States	94040
50	Sutter Cancer Research Consortium	Novato	California	United States	94945
51	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
52	Bay Area Tumor Institute	Oakland	California	United States	94609
53	Hematology and Oncology Associates-Oakland	Oakland	California	United States	94609
54	Kaiser Permanente Oakland-Broadway	Oakland	California	United States	94611
55	Kaiser Permanente-Oakland	Oakland	California	United States	94611
56	UC Irvine Health/Chao Family Comprehensive Cancer Center	Orange	California	United States	92868
57	Palo Alto Medical Foundation Health Care	Palo Alto	California	United States	94301
58	Kaiser Permanente - Panorama City	Panorama City	California	United States	91402
59	Keck Medical Center of USC Pasadena	Pasadena	California	United States	91105
60	PCR Oncology	Pismo Beach	California	United States	93449
61	Kaiser Permanente-Rancho Cordova Cancer Center	Rancho Cordova	California	United States	95670
62	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
63	Kaiser Permanente-Richmond	Richmond	California	United States	94801
64	Kaiser Permanente-Riverside	Riverside	California	United States	92505
65	Rohnert Park Cancer Center	Rohnert Park	California	United States	94928
66	Kaiser Permanente-Roseville	Roseville	California	United States	95661
67	Sutter Cancer Centers Radiation Oncology Services-Roseville	Roseville	California	United States	95661
68	Sutter Roseville Medical Center	Roseville	California	United States	95661
69	The Permanente Medical Group-Roseville Radiation Oncology	Roseville	California	United States	95678
70	Sutter General Hospital	Sacramento	California	United States	95816
71	University of California Davis Comprehensive Cancer Center	Sacramento	California	United States	95817
72	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
73	South Sacramento Cancer Center	Sacramento	California	United States	95823
74	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
75	Salinas Valley Memorial	Salinas	California	United States	93901
76	Kaiser Permanente-San Diego Mission	San Diego	California	United States	92108
77	Kaiser Permanente-San Diego Zion	San Diego	California	United States	92120
78	California Pacific Medical Center-Pacific Campus	San Francisco	California	United States	94115
79	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
80	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
81	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
82	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
83	Kaiser Permanente San Leandro	San Leandro	California	United States	94577
84	Kaiser Permanente-San Marcos	San Marcos	California	United States	92069
85	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
86	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
87	Palo Alto Medical Foundation-Santa Cruz	Santa Cruz	California	United States	95065
88	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
89	Sutter Pacific Medical Foundation	Santa Rosa	California	United States	95403
90	Kaiser Permanente Cancer Treatment Center	South San Francisco	California	United States	94080
91	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
92	Kaiser Permanente-Stockton	Stockton	California	United States	95210
93	Palo Alto Medical Foundation-Sunnyvale	Sunnyvale	California	United States	94086
94	Gene Upshaw Memorial Tahoe Forest Cancer Center	Truckee	California	United States	96161
95	Sutter Cancer Centers Radiation Oncology Services-Vacaville	Vacaville	California	United States	95687
96	Kaiser Permanente Medical Center-Vacaville	Vacaville	California	United States	95688
97	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
98	Sutter Solano Medical Center/Cancer Center	Vallejo	California	United States	94589
99	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
100	Kaiser Permanente	Woodland Hills	California	United States	91367
101	Rocky Mountain Cancer Centers-Aurora	Aurora	Colorado	United States	80012
102	The Medical Center of Aurora	Aurora	Colorado	United States	80012
103	University of Colorado Cancer Center - Anschutz Cancer Pavilion	Aurora	Colorado	United States	80045
104	Boulder Community Hospital	Boulder	Colorado	United States	80301
105	Rocky Mountain Cancer Centers-Boulder	Boulder	Colorado	United States	80304
106	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
107	Rocky Mountain Cancer Centers-Penrose	Colorado Springs	Colorado	United States	80907
108	Memorial Hospital Colorado Springs	Colorado Springs	Colorado	United States	80909
109	Denver Health Medical Center	Denver	Colorado	United States	80204
110	Porter Adventist Hospital	Denver	Colorado	United States	80210
111	Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
112	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
113	Rocky Mountain Cancer Centers-Midtown	Denver	Colorado	United States	80218
114	SCL Health Saint Joseph Hospital	Denver	Colorado	United States	80218
115	Rocky Mountain Cancer Centers-Rose	Denver	Colorado	United States	80220
116	Rose Medical Center	Denver	Colorado	United States	80220
117	Colorado Cancer Research Program NCORP	Denver	Colorado	United States	80222
118	Mercy Medical Center	Durango	Colorado	United States	81301
119	Southwest Oncology PC	Durango	Colorado	United States	81301
120	Comprehensive Cancer Care and Research Institute of Colorado LLC	Englewood	Colorado	United States	80113
121	Swedish Medical Center	Englewood	Colorado	United States	80113
122	Poudre Valley Hospital	Fort Collins	Colorado	United States	80524
123	Mountain Blue Cancer Care Center	Golden	Colorado	United States	80401
124	National Jewish Health-Western Hematology Oncology	Golden	Colorado	United States	80401
125	North Colorado Medical Center	Greeley	Colorado	United States	80631
126	Rocky Mountain Cancer Centers-Greenwood Village	Greenwood Village	Colorado	United States	80111
127	Rocky Mountain Cancer Centers-Lakewood	Lakewood	Colorado	United States	80228
128	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
129	Rocky Mountain Cancer Centers-Littleton	Littleton	Colorado	United States	80120
130	Littleton Adventist Hospital	Littleton	Colorado	United States	80122
131	Rocky Mountain Cancer Centers-Sky Ridge	Lone Tree	Colorado	United States	80124
132	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
133	Longmont United Hospital	Longmont	Colorado	United States	80501
134	Rocky Mountain Cancer Centers-Longmont	Longmont	Colorado	United States	80501
135	McKee Medical Center	Loveland	Colorado	United States	80539
136	Parker Adventist Hospital	Parker	Colorado	United States	80138
137	Rocky Mountain Cancer Centers-Parker	Parker	Colorado	United States	80138
138	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
139	Rocky Mountain Cancer Centers - Pueblo	Pueblo	Colorado	United States	81008
140	Rocky Mountain Cancer Centers-Thornton	Thornton	Colorado	United States	80260
141	SCL Health Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
142	Smilow Cancer Hospital-Derby Care Center	Derby	Connecticut	United States	06418
143	Smilow Cancer Hospital Care Center-Fairfield	Fairfield	Connecticut	United States	06824
144	Greenwich Hospital	Greenwich	Connecticut	United States	06830
145	Medical Oncology and Hematology Group PC-Guilford	Guilford	Connecticut	United States	06437
146	Smilow Cancer Hospital Care Center at Saint Francis	Hartford	Connecticut	United States	06105
147	Middlesex Hospital	Middletown	Connecticut	United States	06457
148	Yale University	New Haven	Connecticut	United States	06520
149	Yale-New Haven Hospital North Haven Medical Center	North Haven	Connecticut	United States	06473
150	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
151	Smilow Cancer Hospital-Orange Care Center	Orange	Connecticut	United States	06477
152	Charlotte Hungerford Hospital Center for Cancer Care	Torrington	Connecticut	United States	06790
153	Smilow Cancer Hospital Care Center-Trumbull	Trumbull	Connecticut	United States	06611
154	Smilow Cancer Hospital-Waterbury Care Center	Waterbury	Connecticut	United States	06708
155	Beebe Medical Center	Lewes	Delaware	United States	19958
156	Christiana Gynecologic Oncology LLC	Newark	Delaware	United States	19713
157	Delaware Clinical and Laboratory Physicians PA	Newark	Delaware	United States	19713
158	Helen F Graham Cancer Center	Newark	Delaware	United States	19713
159	Medical Oncology Hematology Consultants PA	Newark	Delaware	United States	19713
160	Regional Hematology and Oncology PA	Newark	Delaware	United States	19713
161	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
162	Beebe Health Campus	Rehoboth Beach	Delaware	United States	19971
163	Nanticoke Memorial Hospital	Seaford	Delaware	United States	19973
164	Christiana Care Health System-Wilmington Hospital	Wilmington	Delaware	United States	19801
165	Florida Hospital Cancer Institute Altamonte	Altamonte Springs	Florida	United States	32701
166	University of Florida	Gainesville	Florida	United States	32610
167	Florida Hospital Kissimmee	Kissimmee	Florida	United States	34744
168	Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
169	Florida Hospital Orlando	Orlando	Florida	United States	32803
170	Florida Urology Associates-Orlando	Orlando	Florida	United States	32803
171	UF Cancer Center at Orlando Health	Orlando	Florida	United States	32806
172	Florida Hospital East Orlando	Orlando	Florida	United States	32822
173	Florida Hospital Cancer Institute Winter Park	Winter Park	Florida	United States	32792
174	Northside Hospital	Atlanta	Georgia	United States	30342
175	John B Amos Cancer Center	Columbus	Georgia	United States	31904
176	Memorial University Medical Center	Savannah	Georgia	United States	31404
177	Summit Cancer Care-Memorial	Savannah	Georgia	United States	31404
178	Lewis Cancer and Research Pavilion at Saint Joseph's/Candler	Savannah	Georgia	United States	31405
179	Low Country Cancer Care Associates PC	Savannah	Georgia	United States	31405
180	Hawaii Oncology Inc-Pali Momi	'Aiea	Hawaii	United States	96701
181	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
182	The Cancer Center of Hawaii-Leeward	'Ewa Beach	Hawaii	United States	96706
183	Hawaii Cancer Care Inc-POB II	Honolulu	Hawaii	United States	96813
184	Queen's Medical Center	Honolulu	Hawaii	United States	96813
185	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
186	University of Hawaii Cancer Center	Honolulu	Hawaii	United States	96813
187	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii	United States	96817
188	Hawaii Oncology Inc-Kuakini	Honolulu	Hawaii	United States	96817
189	Kuakini Medical Center	Honolulu	Hawaii	United States	96817
190	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
191	Kaiser Permanente Moanalua Medical Center	Honolulu	Hawaii	United States	96819
192	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
193	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii	United States	96766
194	Saint Alphonsus Cancer Care Center-Boise	Boise	Idaho	United States	83706
195	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
196	Saint Luke's Mountain States Tumor Institute - Fruitland	Fruitland	Idaho	United States	83619
197	Saint Luke's Mountain States Tumor Institute - Meridian	Meridian	Idaho	United States	83642
198	Saint Luke's Mountain States Tumor Institute - Nampa	Nampa	Idaho	United States	83686
199	Saint Luke's Mountain States Tumor Institute-Twin Falls	Twin Falls	Idaho	United States	83301
200	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
201	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
202	Illinois CancerCare-Bloomington	Bloomington	Illinois	United States	61704
203	Illinois CancerCare-Canton	Canton	Illinois	United States	61520
204	Memorial Hospital of Carbondale	Carbondale	Illinois	United States	62902
205	Illinois CancerCare-Carthage	Carthage	Illinois	United States	62321
206	Centralia Oncology Clinic	Centralia	Illinois	United States	62801
207	Northwestern University	Chicago	Illinois	United States	60611
208	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612
209	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
210	Carle on Vermilion	Danville	Illinois	United States	61832
211	Cancer Care Center of Decatur	Decatur	Illinois	United States	62526
212	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
213	Carle Physician Group-Effingham	Effingham	Illinois	United States	62401
214	Crossroads Cancer Center	Effingham	Illinois	United States	62401
215	Illinois CancerCare-Eureka	Eureka	Illinois	United States	61530
216	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
217	Illinois CancerCare-Galesburg	Galesburg	Illinois	United States	61401
218	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
219	NorthShore University HealthSystem-Glenbrook Hospital	Glenview	Illinois	United States	60026
220	NorthShore University HealthSystem-Highland Park Hospital	Highland Park	Illinois	United States	60035
221	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
222	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois	United States	61443
223	Illinois CancerCare-Macomb	Macomb	Illinois	United States	61455
224	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois	United States	61938
225	Loyola University Medical Center	Maywood	Illinois	United States	60153
226	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
227	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
228	UC Comprehensive Cancer Center at Silver Cross	New Lenox	Illinois	United States	60451
229	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
230	Radiation Oncology of Northern Illinois	Ottawa	Illinois	United States	61350
231	Illinois CancerCare-Pekin	Pekin	Illinois	United States	61554
232	OSF Saint Francis Radiation Oncology at Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
233	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
234	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
235	OSF Saint Francis Radiation Oncology at Peoria Cancer Center	Peoria	Illinois	United States	61615
236	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
237	Illinois CancerCare-Peru	Peru	Illinois	United States	61354
238	Valley Radiation Oncology	Peru	Illinois	United States	61354
239	Edward Hospital/Cancer Center?Plainfield	Plainfield	Illinois	United States	60585
240	Illinois CancerCare-Princeton	Princeton	Illinois	United States	61356
241	North Shore Medical Center	Skokie	Illinois	United States	60076
242	Central Illinois Hematology Oncology Center	Springfield	Illinois	United States	62702
243	Southern Illinois University School of Medicine	Springfield	Illinois	United States	62702
244	Springfield Clinic	Springfield	Illinois	United States	62702
245	Memorial Medical Center	Springfield	Illinois	United States	62781
246	Cancer Care Specialists of Illinois-Swansea	Swansea	Illinois	United States	62226
247	Carle Cancer Center	Urbana	Illinois	United States	61801
248	The Carle Foundation Hospital	Urbana	Illinois	United States	61801
249	Rush-Copley Healthcare Center	Yorkville	Illinois	United States	60560
250	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
251	Woodland Cancer Care Center	Michigan City	Indiana	United States	46360
252	Memorial Regional Cancer Center Day Road	Mishawaka	Indiana	United States	46544
253	Reid Health	Richmond	Indiana	United States	47374
254	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
255	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
256	Porter Memorial Hospital	Valparaiso	Indiana	United States	46383
257	Mary Greeley Medical Center	Ames	Iowa	United States	50010
258	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
259	McFarland Clinic PC-Boone	Boone	Iowa	United States	50036
260	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
261	Mercy Cancer Center-West Lakes	Clive	Iowa	United States	50325
262	Alegent Health Mercy Hospital	Council Bluffs	Iowa	United States	51503
263	Greater Regional Medical Center	Creston	Iowa	United States	50801
264	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
265	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
266	McFarland Clinic PC-Trinity Cancer Center	Fort Dodge	Iowa	United States	50501
267	McFarland Clinic PC-Jefferson	Jefferson	Iowa	United States	50129
268	McFarland Clinic PC-Marshalltown	Marshalltown	Iowa	United States	50158
269	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
270	Story County Medical Center-South Campus	Nevada	Iowa	United States	50201
271	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101
272	Mercy Medical Center-West Lakes	West Des Moines	Iowa	United States	50266
273	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
274	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
275	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
276	Newman Regional Health	Emporia	Kansas	United States	66801
277	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
278	Saint Catherine Hospital	Garden City	Kansas	United States	67846
279	Saint Rose Ambulatory and Surgery Center	Great Bend	Kansas	United States	67530
280	Hays Medical Center	Hays	Kansas	United States	67601
281	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
282	University of Kansas Cancer Center-West	Kansas City	Kansas	United States	66112
283	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
284	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
285	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
286	Cancer Center of Kansas-Liberal	Liberal	Kansas	United States	67905
287	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
288	Olathe Medical Center	Olathe	Kansas	United States	66061
289	University of Kansas Cancer Center-Overland Park	Overland Park	Kansas	United States	66210
290	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
291	Via Christi Hospital-Pittsburg	Pittsburg	Kansas	United States	66762
292	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
293	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
294	Salina Regional Health Center	Salina	Kansas	United States	67401
295	Saint Francis Hospital and Medical Center - Topeka	Topeka	Kansas	United States	66606
296	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
297	Associates In Womens Health	Wichita	Kansas	United States	67208
298	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
299	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
300	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
301	Wichita NCI Community Oncology Research Program	Wichita	Kansas	United States	67214
302	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
303	Flaget Memorial Hospital	Bardstown	Kentucky	United States	40004
304	Commonwealth Cancer Center-Corbin	Corbin	Kentucky	United States	40701
305	Oncology Hematology Care Inc-Crestview	Crestview Hills	Kentucky	United States	41017
306	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky	United States	40504
307	Saint Joseph Hospital East	Lexington	Kentucky	United States	40509
308	Jewish Hospital	Louisville	Kentucky	United States	40202
309	Saints Mary and Elizabeth Hospital	Louisville	Kentucky	United States	40215
310	Jewish Hospital Medical Center Northeast	Louisville	Kentucky	United States	40245
311	Jewish Hospital Medical Center South	Shepherdsville	Kentucky	United States	40165
312	Christus Saint Frances Cabrini Hospital	Alexandria	Louisiana	United States	71301
313	LSU Health Baton Rouge-North Clinic	Baton Rouge	Louisiana	United States	70805
314	Louisiana Hematology Oncology Associates LLC	Baton Rouge	Louisiana	United States	70809
315	Medical Oncology LLC	Baton Rouge	Louisiana	United States	70809
316	Mary Bird Cancer Center/Saint Tammany Parish	Covington	Louisiana	United States	70433
317	Mary Bird Perkins Cancer Center/Terrebonne General Medical Center	Houma	Louisiana	United States	70360
318	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
319	Harold Alfond Center for Cancer Care	Augusta	Maine	United States	04330
320	Eastern Maine Medical Center	Bangor	Maine	United States	04401
321	Lafayette Family Cancer Center-EMMC	Brewer	Maine	United States	04412
322	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
323	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
324	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
325	Northwest Hospital Center	Randallstown	Maryland	United States	21133
326	Peninsula Regional Medical Center	Salisbury	Maryland	United States	21801
327	Beverly Hospital	Beverly	Massachusetts	United States	01915
328	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
329	Addison Gilbert Hospital	Gloucester	Massachusetts	United States	01930
330	Baystate Medical Center	Springfield	Massachusetts	United States	01199
331	Hickman Cancer Center	Adrian	Michigan	United States	49221
332	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
333	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
334	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
335	McLaren-Bay Region	Bay City	Michigan	United States	48706
336	Henry Ford Cancer Institute¿Downriver	Brownstown	Michigan	United States	48183
337	Great Lakes Cancer Institute	Clarkston	Michigan	United States	48346
338	Henry Ford Macomb Hospital-Clinton Township	Clinton Township	Michigan	United States	48038
339	Beaumont Hospital-Dearborn	Dearborn	Michigan	United States	48124
340	Henry Ford Medical Center-Fairlane	Dearborn	Michigan	United States	48126
341	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
342	Henry Ford Hospital	Detroit	Michigan	United States	48202
343	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
344	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49829
345	Weisberg Cancer Treatment Center	Farmington Hills	Michigan	United States	48334
346	Hurley Medical Center	Flint	Michigan	United States	48502
347	Genesys Hurley Cancer Institute	Flint	Michigan	United States	48503
348	Singh and Arora Hematology Oncology PC	Flint	Michigan	United States	48532
349	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
350	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
351	Allegiance Health	Jackson	Michigan	United States	49201
352	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
353	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
354	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007
355	McLaren-Greater Lansing	Lansing	Michigan	United States	48910
356	Sparrow Hospital	Lansing	Michigan	United States	48912
357	McLaren Cancer Institute-Lapeer Region	Lapeer	Michigan	United States	48446
358	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
359	Monroe Cancer Center	Monroe	Michigan	United States	48162
360	Toledo Clinic Cancer Centers-Monroe	Monroe	Michigan	United States	48162
361	McLaren Cancer Institute-Macomb	Mount Clemens	Michigan	United States	48043
362	McLaren Cancer Institute-Central Michigan	Mount Pleasant	Michigan	United States	48858
363	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
364	Lakeland Community Hospital	Niles	Michigan	United States	49120
365	Assarian Cancer Center	Novi	Michigan	United States	48374-1236
366	Henry Ford Medical Center-Columbus	Novi	Michigan	United States	48377
367	McLaren Cancer Institute-Northern Michigan	Petoskey	Michigan	United States	49770
368	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341
369	Lake Huron Medical Center	Port Huron	Michigan	United States	48060
370	Spectrum Health Reed City Hospital	Reed City	Michigan	United States	49677
371	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
372	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
373	Marie Yeager Cancer Center	Saint Joseph	Michigan	United States	49085
374	Providence Hospital-Southfield Cancer Center	Southfield	Michigan	United States	48075
375	Munson Medical Center	Traverse City	Michigan	United States	49684
376	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
377	Henry Ford West Bloomfield Hospital	West Bloomfield	Michigan	United States	48322
378	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
379	Essentia Health Saint Joseph's Medical Center	Brainerd	Minnesota	United States	56401
380	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
381	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
382	Essentia Health Cancer Center	Duluth	Minnesota	United States	55805
383	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
384	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
385	Saint Luke's Hospital of Duluth	Duluth	Minnesota	United States	55805
386	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
387	Lake Region Healthcare Corporation-Cancer Care	Fergus Falls	Minnesota	United States	56537
388	Unity Hospital	Fridley	Minnesota	United States	55432
389	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
390	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
391	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
392	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
393	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
394	Health Partners Inc	Minneapolis	Minnesota	United States	55454
395	New Ulm Medical Center	New Ulm	Minnesota	United States	56073
396	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
397	Mayo Clinic	Rochester	Minnesota	United States	55905
398	Coborn Cancer Center at Saint Cloud Hospital	Saint Cloud	Minnesota	United States	56303
399	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
400	Regions Hospital	Saint Paul	Minnesota	United States	55101
401	United Hospital	Saint Paul	Minnesota	United States	55102
402	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
403	Lakeview Hospital	Stillwater	Minnesota	United States	55082
404	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
405	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
406	Minnesota Oncology Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
407	Hattiesburg Clinic - Hematology/Oncology Clinic	Hattiesburg	Mississippi	United States	39401
408	Forrest General Hospital / Cancer Center	Hattiesburg	Mississippi	United States	39404
409	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
410	Singing River Hospital	Pascagoula	Mississippi	United States	39581
411	Central Care Cancer Center-Carrie J Babb Cancer Center	Bolivar	Missouri	United States	65613
412	Parkland Health Center-Bonne Terre	Bonne Terre	Missouri	United States	63628
413	CoxHealth Cancer Center	Branson	Missouri	United States	65616
414	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
415	Southeast Cancer Center	Cape Girardeau	Missouri	United States	63703
416	Saint Luke's Hospital	Chesterfield	Missouri	United States	63017
417	Barnes-Jewish West County Hospital	Creve Coeur	Missouri	United States	63141
418	Capital Region Medical Center-Goldschmidt Cancer Center	Jefferson City	Missouri	United States	65109
419	Freeman Health System	Joplin	Missouri	United States	64804
420	Mercy Hospital-Joplin	Joplin	Missouri	United States	64804
421	Truman Medical Center	Kansas City	Missouri	United States	64108
422	The University of Kansas Cancer Center-South	Kansas City	Missouri	United States	64131
423	The University of Kansas Cancer Center-North	Kansas City	Missouri	United States	64154
424	The University of Kansas Cancer Center-Lee's Summit	Lee's Summit	Missouri	United States	64064
425	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri	United States	65401
426	Saint John's Clinic-Rolla-Cancer and Hematology	Rolla	Missouri	United States	65401
427	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
428	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
429	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
430	Mercy Hospital Saint Louis	Saint Louis	Missouri	United States	63141
431	Siteman Cancer Center - Saint Peters	Saint Peters	Missouri	United States	63376
432	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri	United States	63670
433	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
434	CoxHealth South Hospital	Springfield	Missouri	United States	65807
435	Missouri Baptist Sullivan Hospital	Sullivan	Missouri	United States	63080
436	Missouri Baptist Outpatient Center-Sunset Hills	Sunset Hills	Missouri	United States	63127
437	CHI Health Saint Francis	Grand Island	Nebraska	United States	68803
438	Heartland Hematology and Oncology	Kearney	Nebraska	United States	68845
439	CHI Health Good Samaritan	Kearney	Nebraska	United States	68847
440	Nebraska Hematology and Oncology	Lincoln	Nebraska	United States	68506
441	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
442	Saint Elizabeth Regional Medical Center	Lincoln	Nebraska	United States	68510
443	Southeast Nebraska Cancer Center	Lincoln	Nebraska	United States	68510
444	Faith Regional Medical Offices West	Norfolk	Nebraska	United States	68701
445	Great Plains Regional Medical Center	North Platte	Nebraska	United States	69103
446	Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
447	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
448	Hemotology and Oncology Consultants PC	Omaha	Nebraska	United States	68122
449	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
450	Oncology Hematology West	Omaha	Nebraska	United States	68124
451	Alegent Health Lakeside Hospital	Omaha	Nebraska	United States	68130
452	Oncology Hematology West PC	Omaha	Nebraska	United States	68130
453	Creighton University Medical Center	Omaha	Nebraska	United States	68131
454	Midlands Community Hospital	Papillion	Nebraska	United States	68046
455	Regional West Medical Center	Scottsbluff	Nebraska	United States	69361
456	Cancer and Blood Specialists-Henderson	Henderson	Nevada	United States	89052
457	Comprehensive Cancer Centers of Nevada - Henderson	Henderson	Nevada	United States	89052
458	Las Vegas Cancer Center-Henderson	Henderson	Nevada	United States	89052
459	21st Century Oncology - Henderson	Henderson	Nevada	United States	89074
460	Comprehensive Cancer Centers of Nevada-Southeast Henderson	Henderson	Nevada	United States	89074
461	Cancer and Blood Specialists-Shadow	Las Vegas	Nevada	United States	89106
462	Radiation Oncology Centers of Nevada Central	Las Vegas	Nevada	United States	89106
463	21st Century Oncology	Las Vegas	Nevada	United States	89109
464	HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway	Las Vegas	Nevada	United States	89109
465	HealthCare Partners Medical Group Oncology/Hematology-San Martin	Las Vegas	Nevada	United States	89113
466	Radiation Oncology Centers of Nevada Southeast	Las Vegas	Nevada	United States	89119
467	Cancer Therapy and Integrative Medicine	Las Vegas	Nevada	United States	89121
468	Cancer and Blood Specialists-Tenaya	Las Vegas	Nevada	United States	89128
469	Comprehensive Cancer Centers of Nevada - Northwest	Las Vegas	Nevada	United States	89128
470	HealthCare Partners Medical Group Oncology/Hematology-Tenaya	Las Vegas	Nevada	United States	89128
471	Comprehensive Cancer Centers of Nevada-Summerlin	Las Vegas	Nevada	United States	89144
472	Summerlin Hospital Medical Center	Las Vegas	Nevada	United States	89144
473	Las Vegas Cancer Center-Medical Center	Las Vegas	Nevada	United States	89148-2405
474	21st Century Oncology - Fort Apache	Las Vegas	Nevada	United States	89148
475	Cancer and Blood Specialists-Fort Apache	Las Vegas	Nevada	United States	89148
476	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada	United States	89148
477	HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills	Las Vegas	Nevada	United States	89149
478	Comprehensive Cancer Centers of Nevada - Central Valley	Las Vegas	Nevada	United States	89169
479	21st Century Oncology - Vegas Tenaya	Las Vegas	Nevada	United States	89182
480	Saint Mary's Regional Medical Center	Reno	Nevada	United States	89503
481	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
482	Norris Cotton Cancer Center-Manchester	Manchester	New Hampshire	United States	03102
483	Norris Cotton Cancer Center-Nashua	Nashua	New Hampshire	United States	03063
484	Englewood Hospital and Medical Center	Englewood	New Jersey	United States	07631
485	Virtua Memorial	Mount Holly	New Jersey	United States	08060
486	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
487	The Valley Hospital-Luckow Pavilion	Paramus	New Jersey	United States	07652
488	Valley Hospital	Ridgewood	New Jersey	United States	07450
489	Sparta Cancer Treatment Center	Sparta	New Jersey	United States	07871
490	Inspira Medical Center Vineland	Vineland	New Jersey	United States	08360
491	Virtua Voorhees	Voorhees	New Jersey	United States	08043
492	Valley Health System-Hematology/Oncology	Westwood	New Jersey	United States	07675
493	Inspira Medical Center Woodbury	Woodbury	New Jersey	United States	08096
494	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87102
495	Memorial Medical Center - Las Cruces	Las Cruces	New Mexico	United States	88011
496	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
497	Montefiore Medical Center-Weiler Hospital	Bronx	New York	United States	10461
498	Montefiore Medical Center - Moses Campus	Bronx	New York	United States	10467-2490
499	Arnot Ogden Medical Center/Falck Cancer Center	Elmira	New York	United States	14905
500	Glens Falls Hospital	Glens Falls	New York	United States	12801
501	Weill Medical College of Cornell University	New York	New York	United States	10065
502	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
503	Faxton-Saint Luke's Healthcare	Utica	New York	United States	13502
504	Randolph Hospital	Asheboro	North Carolina	United States	27203
505	Asheville Hematology-Oncology Associates	Asheville	North Carolina	United States	28803
506	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
507	Sampson Radiation Oncology	Clinton	North Carolina	United States	28328
508	Southeastern Medical Oncology Center-Clinton	Clinton	North Carolina	United States	28328
509	Duke University Medical Center	Durham	North Carolina	United States	27710
510	Southeastern Medical Oncology Center-Goldsboro	Goldsboro	North Carolina	United States	27534
511	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
512	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
513	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
514	Hendersonville Hematology and Oncology at Pardee	Hendersonville	North Carolina	United States	28791
515	Margaret R Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
516	Park Ridge Hospital Breast Health Center	Hendersonville	North Carolina	United States	28792
517	Maria Parham Hospital	Henderson	North Carolina	United States	27536
518	Onslow Memorial Hospital	Jacksonville	North Carolina	United States	28546
519	Southeastern Medical Oncology Center-Jacksonville	Jacksonville	North Carolina	United States	28546
520	Kinston Medical Specialists PA	Kinston	North Carolina	United States	28501
521	Scotland Memorial Hospital-Laurinburg Cancer Center	Laurinburg	North Carolina	United States	28352
522	Cone Heath Cancer Center at Mebane	Mebane	North Carolina	United States	27302
523	Annie Penn Memorial Hospital	Reidsville	North Carolina	United States	27320
524	Johnston Memorial Hospital	Smithfield	North Carolina	United States	27577
525	Southeastern Medical Oncology Center-Wilson	Wilson	North Carolina	United States	27893
526	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
527	Essentia Health Cancer Center-South University Clinic	Fargo	North Dakota	United States	58103
528	Roger Maris Cancer Center	Fargo	North Dakota	United States	58122
529	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
530	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
531	Akron General Medical Center	Akron	Ohio	United States	44307
532	Strecker Cancer Center-Belpre	Belpre	Ohio	United States	45714
533	Mercy Medical Center	Canton	Ohio	United States	44708
534	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio	United States	45459
535	Miami Valley Hospital South	Centerville	Ohio	United States	45459
536	Geaugra Hospital	Chardon	Ohio	United States	44024
537	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
538	Oncology Hematology Care Inc-Eden Park	Cincinnati	Ohio	United States	45202
539	Oncology Hematology Care Inc-Mercy West	Cincinnati	Ohio	United States	45211
540	University of Cincinnati/Barrett Cancer Center	Cincinnati	Ohio	United States	45219
541	Good Samaritan Hospital - Cincinnati	Cincinnati	Ohio	United States	45220
542	Oncology Hematology Care Inc - Anderson	Cincinnati	Ohio	United States	45230
543	Oncology Hematology Care Inc-Kenwood	Cincinnati	Ohio	United States	45236
544	Bethesda North Hospital	Cincinnati	Ohio	United States	45242
545	Oncology Hematology Care Inc-Blue Ash	Cincinnati	Ohio	United States	45242
546	TriHealth Cancer Institute-Westside	Cincinnati	Ohio	United States	45247
547	TriHealth Cancer Institute-Anderson	Cincinnati	Ohio	United States	45255
548	Case Western Reserve University	Cleveland	Ohio	United States	44106
549	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
550	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44111
551	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
552	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
553	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
554	Grant Medical Center	Columbus	Ohio	United States	43215
555	The Mark H Zangmeister Center	Columbus	Ohio	United States	43219
556	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
557	Doctors Hospital	Columbus	Ohio	United States	43228
558	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
559	Miami Valley Hospital	Dayton	Ohio	United States	45409
560	Dayton Physicians LLC-Samaritan North	Dayton	Ohio	United States	45415
561	Samaritan North Health Center	Dayton	Ohio	United States	45415
562	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
563	Delaware Radiation Oncology	Delaware	Ohio	United States	43015
564	Grady Memorial Hospital	Delaware	Ohio	United States	43015
565	Mercy Cancer Center-Elyria	Elyria	Ohio	United States	44035
566	Oncology Hematology Care Inc-Healthplex	Fairfield	Ohio	United States	45014
567	Armes Family Cancer Center	Findlay	Ohio	United States	45840
568	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
569	Orion Cancer Care	Findlay	Ohio	United States	45840
570	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
571	Dayton Physicians LLC-Atrium	Franklin	Ohio	United States	45005
572	Dayton Physicians LLC-Wayne	Greenville	Ohio	United States	45331
573	Wayne Hospital	Greenville	Ohio	United States	45331
574	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
575	Greater Dayton Cancer Center	Kettering	Ohio	United States	45409
576	Kettering Medical Center	Kettering	Ohio	United States	45429
577	Fairfield Medical Center	Lancaster	Ohio	United States	43130
578	Saint Rita's Medical Center	Lima	Ohio	United States	45801
579	Cleveland Clinic Cancer Center Mansfield	Mansfield	Ohio	United States	44906
580	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
581	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
582	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
583	Hillcrest Hospital Cancer Center	Mayfield Heights	Ohio	United States	44124
584	Lake University Ireland Cancer Center	Mentor	Ohio	United States	44060
585	Southwest General Health Center Ireland Cancer Center	Middleburg Heights	Ohio	United States	44130
586	Dayton Physicians LLC-Signal Point	Middletown	Ohio	United States	45042
587	Knox Community Hospital	Mount Vernon	Ohio	United States	43050
588	Licking Memorial Hospital	Newark	Ohio	United States	43055
589	Newark Radiation Oncology	Newark	Ohio	United States	43055
590	Saint Charles Hospital	Oregon	Ohio	United States	43616
591	University Hospitals Parma Medical Center	Parma	Ohio	United States	44129
592	Southern Ohio Medical Center	Portsmouth	Ohio	United States	45662
593	Ireland Cancer Center at Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
594	North Coast Cancer Care	Sandusky	Ohio	United States	44870
595	Dayton Physicians LLC-Wilson	Sidney	Ohio	United States	45365
596	Springfield Regional Cancer Center	Springfield	Ohio	United States	45504
597	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
598	Cleveland Clinic Cancer Center Strongsville	Strongsville	Ohio	United States	44136
599	Flower Hospital	Sylvania	Ohio	United States	43560
600	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
601	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
602	Dayton Physicians LLC-Upper Valley	Troy	Ohio	United States	45373
603	Upper Valley Medical Center	Troy	Ohio	United States	45373
604	University Hospitals Sharon Health Center	Wadsworth	Ohio	United States	44281
605	South Pointe Hospital	Warrensville Heights	Ohio	United States	44122
606	University Pointe	West Chester	Ohio	United States	45069
607	Saint Ann's Hospital	Westerville	Ohio	United States	43081
608	UH-Seidman Cancer Center at Saint John Medical Center	Westlake	Ohio	United States	44145
609	Cleveland Clinic Wooster Family Health and Surgery Center	Wooster	Ohio	United States	44691
610	Wright-Patterson Medical Center	Wright-Patterson Air Force Base	Ohio	United States	45433-5529
611	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
612	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma	United States	73505
613	Saint Charles Health System	Bend	Oregon	United States	97701
614	Clackamas Radiation Oncology Center	Clackamas	Oregon	United States	97015
615	Providence Oncology and Hematology Care Southeast	Clackamas	Oregon	United States	97015
616	Bay Area Hospital	Coos Bay	Oregon	United States	97420
617	Providence Newberg Medical Center	Newberg	Oregon	United States	97132
618	Providence Willamette Falls Medical Center	Oregon City	Oregon	United States	97045
619	Providence Portland Medical Center	Portland	Oregon	United States	97213
620	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
621	Kaiser Permanente Northwest	Portland	Oregon	United States	97227
622	Christiana Care Health System-Concord Health Center	Chadds Ford	Pennsylvania	United States	19317
623	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
624	Doylestown Hospital	Doylestown	Pennsylvania	United States	18901
625	PinnacleHealth Cancer Center-Community Campus	Harrisburg	Pennsylvania	United States	17109
626	Geisinger Medical Center-Cancer Center Hazleton	Hazleton	Pennsylvania	United States	18201
627	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033-0850
628	Geisinger Medical Oncology-Lewisburg	Lewisburg	Pennsylvania	United States	17837
629	Lewistown Hospital	Lewistown	Pennsylvania	United States	17044
630	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
631	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
632	Phoenixville Hospital	Phoenixville	Pennsylvania	United States	19460
633	Geisinger Medical Oncology-Pottsville	Pottsville	Pennsylvania	United States	17901
634	Guthrie Medical Group PC-Robert Packer Hospital	Sayre	Pennsylvania	United States	18840
635	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania	United States	18508
636	Geisinger Medical Group	State College	Pennsylvania	United States	16801
637	Reading Hospital	West Reading	Pennsylvania	United States	19611
638	Geisinger Wyoming Valley/Henry Cancer Center	Wilkes-Barre	Pennsylvania	United States	18711
639	Susquehanna Cancer Center	Williamsport	Pennsylvania	United States	17701
640	Roper Hospital	Charleston	South Carolina	United States	29401
641	Charleston Hematology Oncology Associates-Roper	Charleston	South Carolina	United States	29403
642	Lowcountry Hematology Oncology PA-North Charleston	Charleston	South Carolina	United States	29406
643	Bon Secours Saint Francis Hospital	Charleston	South Carolina	United States	29414
644	Charleston Hematology Oncology Associates PA-St. Francis	Charleston	South Carolina	United States	29414
645	Lowcountry Hematology Oncology PA-West Ashley	Charleston	South Carolina	United States	29414
646	Greenville Health System Cancer Institute-Easley	Easley	South Carolina	United States	29640
647	Saint Francis Hospital	Greenville	South Carolina	United States	29601
648	Greenville Health System Cancer Institute-Andrews	Greenville	South Carolina	United States	29605
649	Greenville Health System Cancer Institute-Butternut	Greenville	South Carolina	United States	29605
650	Greenville Health System Cancer Institute-Faris	Greenville	South Carolina	United States	29605
651	Greenville Memorial Hospital	Greenville	South Carolina	United States	29605
652	Saint Francis Cancer Center	Greenville	South Carolina	United States	29607
653	Greenville Health System Cancer Institute-Eastside	Greenville	South Carolina	United States	29615
654	Greenville Health System Cancer Institute-Greer	Greer	South Carolina	United States	29650
655	Lowcountry Hematology Oncology PA-Mount Pleasant	Mount Pleasant	South Carolina	United States	29464
656	Greenville Health System Cancer Institute-Seneca	Seneca	South Carolina	United States	29672
657	Greenville Health System Cancer Institute-Spartanburg	Spartanburg	South Carolina	United States	29307
658	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
659	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
660	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
661	Memorial Hospital	Chattanooga	Tennessee	United States	37404
662	Pulmonary Medicine Center of Chattanooga-Hixson	Hixson	Tennessee	United States	37343
663	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
664	Meharry Medical College	Nashville	Tennessee	United States	37208
665	Memorial GYN Plus	Ooltewah	Tennessee	United States	37363
666	M D Anderson Cancer Center	Houston	Texas	United States	77030
667	Scott and White Healthcare Round Rock	Round Rock	Texas	United States	78665
668	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229
669	Scott and White Memorial Hospital	Temple	Texas	United States	76508
670	Central Vermont Medical Center/National Life Cancer Treatment	Berlin	Vermont	United States	05602
671	University of Vermont Medical Center	Burlington	Vermont	United States	05401
672	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
673	Providence Regional Cancer System-Aberdeen	Aberdeen	Washington	United States	98520
674	Cancer Care Center at Island Hospital	Anacortes	Washington	United States	98221
675	MultiCare Auburn Medical Center	Auburn	Washington	United States	98001
676	Virginia Mason Bainbridge Island Medical Center	Bainbridge Island	Washington	United States	98110
677	Overlake Hospital Medical Center	Bellevue	Washington	United States	98004
678	Swedish Cancer Institute-Eastside Oncology Hematology	Bellevue	Washington	United States	98005
679	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
680	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
681	Harrison Medical Center	Bremerton	Washington	United States	98310
682	Highline Medical Center-Main Campus	Burien	Washington	United States	98166
683	Providence Regional Cancer System-Centralia	Centralia	Washington	United States	98531
684	Swedish Medical Center-Edmonds	Edmonds	Washington	United States	98026
685	Saint Elizabeth Hospital	Enumclaw	Washington	United States	98022
686	Providence Regional Cancer Partnership	Everett	Washington	United States	98201
687	Virginia Mason Federal Way Medical Center	Federal Way	Washington	United States	98002
688	Saint Francis Hospital	Federal Way	Washington	United States	98003
689	Tacoma/Valley Radiation Oncology Centers-Gig Harbor	Gig Harbor	Washington	United States	98332
690	MultiCare Gig Harbor Medical Park	Gig Harbor	Washington	United States	98335
691	Swedish Cancer Institute-Issaquah	Issaquah	Washington	United States	98029
692	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
693	Northwest Cancer Clinic	Kennewick	Washington	United States	99336
694	Seattle Cancer Care Alliance at EvergreenHealth	Kirkland	Washington	United States	98034
695	Providence Regional Cancer System-Lacey	Lacey	Washington	United States	98503
696	Saint Clare Hospital	Lakewood	Washington	United States	98499
697	PeaceHealth Saint John Medical Center	Longview	Washington	United States	98632
698	Virginia Mason Lynnwood Medical Center	Lynnwood	Washington	United States	98036
699	Skagit Valley Hospital Regional Cancer Care Center	Mount Vernon	Washington	United States	98273
700	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
701	Olympic Medical Center	Port Angeles	Washington	United States	98362
702	Jefferson Healthcare	Port Townsend	Washington	United States	98368
703	Harrison HealthPartners Hematology and Oncology-Poulsbo	Poulsbo	Washington	United States	98370
704	Peninsula Cancer Center	Poulsbo	Washington	United States	98370
705	MultiCare Good Samaritan Hospital	Puyallup	Washington	United States	98372
706	Tacoma/Valley Radiation Oncology Centers-Puyallup	Puyallup	Washington	United States	98372
707	Virginia Mason Medical Center	Seattle	Washington	United States	98101
708	Minor and James Medical PLLC	Seattle	Washington	United States	98104
709	Pacific Gynecology Specialists	Seattle	Washington	United States	98104
710	Swedish Medical Center-Ballard Campus	Seattle	Washington	United States	98107
711	Fred Hutchinson Cancer Research Center	Seattle	Washington	United States	98109
712	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109
713	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
714	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
715	University of Washington Medical Center	Seattle	Washington	United States	98195
716	Olympic Medical Cancer Care Center	Sequim	Washington	United States	98384
717	Providence Regional Cancer System-Shelton	Shelton	Washington	United States	98584
718	Rockwood Clinic Cancer Treatment Center-Valley	Spokane Valley	Washington	United States	99216
719	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
720	Rockwood Cancer Treatment Center-DHEC-Downtown	Spokane	Washington	United States	99204
721	Spokane Valley Cancer Center-Mayfair	Spokane	Washington	United States	99208
722	Cancer Care Northwest-Valley	Spokane	Washington	United States	99216
723	Cancer Care Northwest-North Spokane	Spokane	Washington	United States	99218
724	Tacoma/Valley Radiation Oncology Centers-Jackson Hall	Tacoma	Washington	United States	97405
725	Franciscan Research Center-Northwest Medical Plaza	Tacoma	Washington	United States	98405
726	MultiCare Tacoma General Hospital	Tacoma	Washington	United States	98405
727	Northwest Medical Specialties PLLC	Tacoma	Washington	United States	98405
728	Northwest NCI Community Oncology Research Program	Tacoma	Washington	United States	98405
729	Tacoma/Valley Radiation Oncology Centers-Saint Joe's	Tacoma	Washington	United States	98405
730	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
731	Providence Saint Mary Regional Cancer Center	Walla Walla	Washington	United States	99362
732	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801
733	North Star Lodge Cancer Center at Yakima Valley Memorial Hospital	Yakima	Washington	United States	98902
734	Providence Regional Cancer System-Yelm	Yelm	Washington	United States	98597
735	West Virginia University Charleston	Charleston	West Virginia	United States	25304
736	Langlade Hospital and Cancer Center	Antigo	Wisconsin	United States	54409
737	Marshfield Clinic-Chippewa Center	Chippewa Falls	Wisconsin	United States	54729
738	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
739	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
740	Saint Vincent Hospital Cancer Center Green Bay	Green Bay	Wisconsin	United States	54301
741	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
742	Saint Vincent Hospital Cancer Center at Saint Mary's	Green Bay	Wisconsin	United States	54303
743	Gundersen Lutheran Medical Center	La Crosse	Wisconsin	United States	54601
744	Holy Family Memorial Hospital	Manitowoc	Wisconsin	United States	54221
745	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
746	Wheaton Franciscan Healthcare - Saint Joseph	Milwaukee	Wisconsin	United States	53210
747	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
748	ProHealth D N Greenwald Center	Mukwonago	Wisconsin	United States	53149
749	Cancer Center of Western Wisconsin	New Richmond	Wisconsin	United States	54017
750	ProHealth Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin	United States	53066
751	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
752	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
753	HSHS Saint Nicholas Hospital	Sheboygan	Wisconsin	United States	53081
754	Marshfield Clinic Cancer Care at Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
755	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
756	ProHealth Waukesha Memorial Hospital	Waukesha	Wisconsin	United States	53188
757	UW Cancer Center at ProHealth Care	Waukesha	Wisconsin	United States	53188
758	Aspirus Regional Cancer Center	Wausau	Wisconsin	United States	54401
759	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
760	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
761	Aspirus UW Cancer Center	Wisconsin Rapids	Wisconsin	United States	54494
762	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
763	Cheyenne Regional Medical Center-West	Cheyenne	Wyoming	United States	82001

Sponsors and Collaborators

• Southwest Oncology Group
• National Cancer Institute (NCI)
• Roche-Genentech

Investigators

• Principal Investigator: Edmund S Kopetz, M.D., M.D. Anderson

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - Nov 10, 2016

More Information

Publications

None provided.

• Responsible Party: Southwest Oncology Group
• ClinicalTrials.gov Identifier: NCT02164916
• Other Study ID Numbers: S1406; U10CA180888; S1406; NCI-2014-00814
• First Posted: Jun 17, 2014
• Last Update Posted: Dec 30, 2020
• Last Verified: Dec 1, 2020

• Keywords provided by Southwest Oncology Group: BRAF Mutant; Metastatic
• Additional relevant MeSH terms: Colorectal Neoplasms; Antineoplastic Agents, Immunological; Cetuximab; Irinotecan; Camptothecin; Vemurafenib; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G; Mitogens

Study Results

Participant Flow

Arm/Group Title	Arm I (Cetuximab, Irinotecan Hydrochloride)	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO
Period Title: Overall Study
STARTED	52	54
Eligible	50	49
Cross-over to Arm II	24	0
COMPLETED	0	0
NOT COMPLETED	52	54

Baseline Characteristics

Arm/Group Title	Arm I (Cetuximab, Irinotecan Hydrochloride)	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)	Total
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO	Total of all reporting groups
Overall Participants	50	49	99
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	62	60	62
Sex: Female, Male (Count of Participants)
Female	37 74%	21 42.9%	58 58.6%
Male	13 26%	28 57.1%	41 41.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 4%	2 4.1%	4 4%
Not Hispanic or Latino	48 96%	46 93.9%	94 94.9%
Unknown or Not Reported	0 0%	1 2%	1 1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 2%	4 8.2%	5 5.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 2%	1 1%
White	49 98%	43 87.8%	92 92.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 2%	1 1%
Prior treatment with Irinotecan (participants) [Number]
Yes	19 38%	20 40.8%	39 39.4%
No	31 62%	29 59.2%	60 60.6%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	From date of randomization to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression free are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.
Time Frame	Up to 3 years from randomization

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients.

Arm/Group Title	Arm I (Cetuximab, Irinotecan Hydrochloride)	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO
Measure Participants	50	49
Median (95% Confidence Interval) [months]	2.0	4.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Cetuximab, Irinotecan Hydrochloride), Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.48
	Confidence Interval	(2-Sided) 95%; 0.31 to 0.75
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Patients With Grade 3 Through 5 Adverse Events That Are Related to Study Drug
Description	Only adverse events that are possibly, probably or definitely related to study drug are reported.
Time Frame	Up to 3 years

Outcome Measure Data

Analysis Population Description

Eligible patients who received any treatment and were assessed for adverse events are included in this summary.

Arm/Group Title	Cetuximab + Irinotecan	Vemurafenib + Cetuximab + Irinotecan	Crossover: Vemurafenib + Cetuximab + Irinotecan
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	46	46	21
Abdominal pain	1 2%	2 4.1%	0 0%
Alkaline phosphatase increased	2 4%	0 0%	1 1%
Allergic reaction	1 2%	0 0%	0 0%
Anaphylaxis	1 2%	0 0%	0 0%
Anemia	0 0%	6 12.2%	1 1%
Anorexia	2 4%	3 6.1%	0 0%
Arthralgia	0 0%	3 6.1%	0 0%
Arthritis	0 0%	0 0%	1 1%
Blood bilirubin increased	1 2%	0 0%	1 1%
Cardiac disorders - Other, specify	0 0%	0 0%	1 1%
Colitis	0 0%	0 0%	1 1%
Colonic obstruction	1 2%	0 0%	0 0%
Creatinine increased	0 0%	1 2%	0 0%
Dehydration	3 6%	5 10.2%	0 0%
Diarrhea	6 12%	11 22.4%	7 7.1%
Electrocardiogram QT corrected interval prolonged	0 0%	1 2%	1 1%
Fatigue	7 14%	7 14.3%	7 7.1%
Febrile neutropenia	2 4%	5 10.2%	0 0%
Gastric hemorrhage	0 0%	0 0%	1 1%
Generalized muscle weakness	1 2%	1 2%	1 1%
Hyperkalemia	0 0%	0 0%	1 1%
Hypocalcemia	0 0%	0 0%	1 1%
Hypokalemia	1 2%	5 10.2%	2 2%
Hypomagnesemia	2 4%	0 0%	1 1%
Hyponatremia	1 2%	2 4.1%	0 0%
Infusion related reaction	1 2%	1 2%	0 0%
Insomnia	0 0%	0 0%	1 1%
Lower gastrointestinal hemorrhage	0 0%	0 0%	1 1%
Lung infection	0 0%	1 2%	0 0%
Lymphocyte count decreased	0 0%	1 2%	0 0%
Metabolic acidosis	1 2%	0 0%	0 0%
Mucositis oral	0 0%	2 4.1%	0 0%
Myalgia	0 0%	2 4.1%	0 0%
Nausea	1 2%	9 18.4%	1 1%
Neutrophil count decreased	3 6%	15 30.6%	2 2%
Pain	0 0%	1 2%	0 0%
Palmar-plantar erythrodysesthesia syndrome	0 0%	0 0%	1 1%
Pancreatitis	0 0%	1 2%	0 0%
Papulopustular rash	1 2%	0 0%	0 0%
Photosensitivity	0 0%	1 2%	0 0%
Platelet count decreased	0 0%	1 2%	0 0%
Pruritus	1 2%	0 0%	0 0%
Rash acneiform	3 6%	0 0%	0 0%
Rash maculo-papular	0 0%	1 2%	1 1%
Rash pustular	0 0%	1 2%	0 0%
Sepsis	0 0%	2 4.1%	0 0%
Thromboembolic event	0 0%	0 0%	1 1%
Treatment related secondary malignancy	0 0%	0 0%	1 1%
Urinary tract infection	1 2%	0 0%	1 1%
Vomiting	1 2%	5 10.2%	0 0%
Weight loss	1 2%	0 0%	0 0%
White blood cell decreased	0 0%	8 16.3%	2 2%

3. Other Pre-specified Outcome

Title	Overall Survival
Description	From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame	Up to 3 years from randomization

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients

Arm/Group Title	Arm I (Cetuximab, Irinotecan Hydrochloride)	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO
Measure Participants	50	49
Median (95% Confidence Interval) [months]	5.9	9.6

4. Other Pre-specified Outcome

Title	Overall Response Rate
Description	Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time Frame	Up to 3 years from randomization

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients with measurable disease.

Arm/Group Title	Arm I (Cetuximab, Irinotecan Hydrochloride)	Arm II (Cetuximab, Irinotecan Hydrochloride, Vemurafenib)
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm II. cetuximab: Given IV irinotecan hydrochloride: Given IV	Patients receive cetuximab and irinotecan hydrochloride as in Arm I and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. cetuximab: Given IV irinotecan hydrochloride: Given IV vemurafenib: Given PO
Measure Participants	47	44
Partial Response	1 2%	3 6.1%
Unconfirmed Partial Response	1 2%	4 8.2%
Stable/No Response	8 16%	22 44.9%
Increasing Disease	25 50%	7 14.3%
Symptomatic Deterioration	6 12%	1 2%
Assessment Inadequate	6 12%	7 14.3%

5. Other Pre-specified Outcome

Title	Progression-free Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1
Description	From date of Step 3 Crossover registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive without report of progression are censored at date of last contact. Progression is defined as one or more of the following: 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm; unequivocal progression of non-measurable disease in the opinion of the treating physician; appearance of any new lesion/site; and/or death due to disease without prior documentation of progression and without symptomatic deterioration.
Time Frame	Up to 3 years from randomization

Outcome Measure Data

Analysis Population Description

All eligible and analyzable patients.

Arm/Group Title	Crossover: Vemurafenib + Cetuximab + Irinotecan
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	22
Median (95% Confidence Interval) [months]	5.8

6. Other Pre-specified Outcome

Title	Overall Survival in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1
Description	From date of randomization to date of death due to any cause. Patients last known to be alive are censored at date of last contact.
Time Frame	Up to 3 years from randomization

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients

Arm/Group Title	Crossover: Vemurafenib + Cetuximab + Irinotecan
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	22
Median (95% Confidence Interval) [months]	12.1

7. Other Pre-specified Outcome

Title	Overall Response Rate in Patients Who Register to Arm 3 (Crossover) After Disease Progression on Arm 1
Description	Confirmed response (CR) is two or more objective statuses of CR a minimum of four weeks apart documented before progression or symptomatic deterioration. Partial response (PR) is two or more objective statuses of PR or better a minimum of four weeks apart documented before progression or symptomatic deterioration. Unconfirmed CR is one objective status of CR documented before progression or symptomatic deterioration but not qualifying as CR or PR. Unconfirmed PR is one objective status of PR documented before progression or symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR.
Time Frame	Up to 3 years from randomization

Outcome Measure Data

Analysis Population Description

Eligible and analyzable patients with measurable disease.

Arm/Group Title	Crossover: Vemurafenib + Cetuximab + Irinotecan
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Measure Participants	18
Partial Response	2 4%
Unconfirmed Partial Response	1 2%
Stable/No Response	10 20%
Increasing Disease	5 10%

Adverse Events

Time Frame	Up to 3 years
Adverse Event Reporting Description	Eligible patients who received any treatment and were assessed for adverse events are included in the adverse event summaries.
Arm/Group Title	Cetuximab + Irinotecan		Vemurafenib + Cetuximab + Irinotecan		Crossover: Vemurafenib + Cetuximab + Irinotecan
Arm/Group Description	Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.		Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.		Patients receive cetuximab IV and irinotecan hydrochloride IV on days 1 and 14, and vemurafenib PO BID on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
All Cause Mortality
	Cetuximab + Irinotecan		Vemurafenib + Cetuximab + Irinotecan		Crossover: Vemurafenib + Cetuximab + Irinotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/46 (6.5%)		4/46 (8.7%)		2/21 (9.5%)
Serious Adverse Events
	Cetuximab + Irinotecan		Vemurafenib + Cetuximab + Irinotecan		Crossover: Vemurafenib + Cetuximab + Irinotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/46 (6.5%)		25/46 (54.3%)		10/21 (47.6%)
Blood and lymphatic system disorders
Anemia	0/46 (0%)		4/46 (8.7%)		0/21 (0%)
Febrile neutropenia	1/46 (2.2%)		4/46 (8.7%)		0/21 (0%)
Cardiac disorders
Atrial flutter	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Cardiac disorders-Other	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Pericardial effusion	1/46 (2.2%)		0/46 (0%)		0/21 (0%)
Sinus tachycardia	1/46 (2.2%)		0/46 (0%)		0/21 (0%)
Gastrointestinal disorders
Abdominal pain	0/46 (0%)		4/46 (8.7%)		1/21 (4.8%)
Ascites	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Colitis	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Colonic obstruction	1/46 (2.2%)		0/46 (0%)		1/21 (4.8%)
Colonic perforation	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Constipation	0/46 (0%)		1/46 (2.2%)		1/21 (4.8%)
Diarrhea	0/46 (0%)		5/46 (10.9%)		0/21 (0%)
Duodenal hemorrhage	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Hemorrhoidal hemorrhage	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Jejunal obstruction	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Lower gastrointestinal hemorrhage	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Nausea	0/46 (0%)		5/46 (10.9%)		1/21 (4.8%)
Pancreatitis	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Rectal hemorrhage	0/46 (0%)		1/46 (2.2%)		1/21 (4.8%)
Small intestinal obstruction	0/46 (0%)		5/46 (10.9%)		0/21 (0%)
Vomiting	0/46 (0%)		4/46 (8.7%)		1/21 (4.8%)
General disorders
Death NOS	1/46 (2.2%)		0/46 (0%)		1/21 (4.8%)
Fatigue	0/46 (0%)		3/46 (6.5%)		1/21 (4.8%)
Fever	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Infections and infestations
Lung infection	0/46 (0%)		2/46 (4.3%)		1/21 (4.8%)
Sepsis	0/46 (0%)		4/46 (8.7%)		0/21 (0%)
Urinary tract infection	0/46 (0%)		2/46 (4.3%)		1/21 (4.8%)
Investigations
Alanine aminotransferase increased	0/46 (0%)		1/46 (2.2%)		2/21 (9.5%)
Alkaline phosphatase increased	0/46 (0%)		2/46 (4.3%)		2/21 (9.5%)
Aspartate aminotransferase increased	0/46 (0%)		1/46 (2.2%)		2/21 (9.5%)
Blood bilirubin increased	1/46 (2.2%)		1/46 (2.2%)		2/21 (9.5%)
Electrocardiogram QT corrected interval prolonged	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Neutrophil count decreased	0/46 (0%)		3/46 (6.5%)		0/21 (0%)
White blood cell decreased	0/46 (0%)		2/46 (4.3%)		0/21 (0%)
Metabolism and nutrition disorders
Anorexia	0/46 (0%)		2/46 (4.3%)		0/21 (0%)
Dehydration	0/46 (0%)		5/46 (10.9%)		0/21 (0%)
Hyponatremia	0/46 (0%)		2/46 (4.3%)		0/21 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified - Other	2/46 (4.3%)		2/46 (4.3%)		1/21 (4.8%)
Treatment related secondary malignancy	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Renal and urinary disorders
Acute kidney injury	1/46 (2.2%)		1/46 (2.2%)		0/21 (0%)
Renal calculi	0/46 (0%)		0/46 (0%)		1/21 (4.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Pleural effusion	0/46 (0%)		1/46 (2.2%)		1/21 (4.8%)
Respiratory failure	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Skin and subcutaneous tissue disorders
Skin and subcutaneous tissue disorders - Other	0/46 (0%)		1/46 (2.2%)		0/21 (0%)
Vascular disorders
Thromboembolic event	1/46 (2.2%)		1/46 (2.2%)		1/21 (4.8%)
Other (Not Including Serious) Adverse Events
	Cetuximab + Irinotecan		Vemurafenib + Cetuximab + Irinotecan		Crossover: Vemurafenib + Cetuximab + Irinotecan
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	45/46 (97.8%)		41/46 (89.1%)		21/21 (100%)
Blood and lymphatic system disorders
Anemia	11/46 (23.9%)		21/46 (45.7%)		9/21 (42.9%)
Eye disorders
Blurred vision	1/46 (2.2%)		4/46 (8.7%)		1/21 (4.8%)
Conjunctivitis	1/46 (2.2%)		0/46 (0%)		2/21 (9.5%)
Eye disorders-Other	1/46 (2.2%)		3/46 (6.5%)		1/21 (4.8%)
Gastrointestinal disorders
Abdominal distension	2/46 (4.3%)		0/46 (0%)		2/21 (9.5%)
Abdominal pain	19/46 (41.3%)		18/46 (39.1%)		5/21 (23.8%)
Colonic obstruction	3/46 (6.5%)		0/46 (0%)		1/21 (4.8%)
Constipation	11/46 (23.9%)		3/46 (6.5%)		4/21 (19%)
Diarrhea	27/46 (58.7%)		28/46 (60.9%)		16/21 (76.2%)
Dyspepsia	2/46 (4.3%)		3/46 (6.5%)		1/21 (4.8%)
Hemorrhoids	3/46 (6.5%)		1/46 (2.2%)		0/21 (0%)
Mucositis oral	7/46 (15.2%)		19/46 (41.3%)		5/21 (23.8%)
Nausea	27/46 (58.7%)		27/46 (58.7%)		16/21 (76.2%)
Vomiting	14/46 (30.4%)		21/46 (45.7%)		6/21 (28.6%)
General disorders
Edema limbs	3/46 (6.5%)		8/46 (17.4%)		4/21 (19%)
Fatigue	31/46 (67.4%)		32/46 (69.6%)		16/21 (76.2%)
Fever	2/46 (4.3%)		9/46 (19.6%)		2/21 (9.5%)
Infusion related reaction	4/46 (8.7%)		3/46 (6.5%)		1/21 (4.8%)
Pain	3/46 (6.5%)		4/46 (8.7%)		4/21 (19%)
Infections and infestations
Urinary tract infection	2/46 (4.3%)		0/46 (0%)		2/21 (9.5%)
Injury, poisoning and procedural complications
Bruising	0/46 (0%)		3/46 (6.5%)		1/21 (4.8%)
Fall	3/46 (6.5%)		0/46 (0%)		1/21 (4.8%)
Investigations
Alanine aminotransferase increased	10/46 (21.7%)		3/46 (6.5%)		4/21 (19%)
Alkaline phosphatase increased	11/46 (23.9%)		7/46 (15.2%)		7/21 (33.3%)
Aspartate aminotransferase increased	12/46 (26.1%)		4/46 (8.7%)		5/21 (23.8%)
Blood bilirubin increased	3/46 (6.5%)		7/46 (15.2%)		2/21 (9.5%)
Creatinine increased	1/46 (2.2%)		4/46 (8.7%)		0/21 (0%)
INR increased	0/46 (0%)		0/46 (0%)		2/21 (9.5%)
Lymphocyte count decreased	1/46 (2.2%)		4/46 (8.7%)		3/21 (14.3%)
Neutrophil count decreased	11/46 (23.9%)		20/46 (43.5%)		8/21 (38.1%)
Platelet count decreased	5/46 (10.9%)		3/46 (6.5%)		0/21 (0%)
Weight loss	6/46 (13%)		13/46 (28.3%)		3/21 (14.3%)
White blood cell decreased	8/46 (17.4%)		15/46 (32.6%)		5/21 (23.8%)
Metabolism and nutrition disorders
Anorexia	13/46 (28.3%)		14/46 (30.4%)		5/21 (23.8%)
Dehydration	10/46 (21.7%)		2/46 (4.3%)		5/21 (23.8%)
Hyperglycemia	6/46 (13%)		5/46 (10.9%)		4/21 (19%)
Hypoalbuminemia	11/46 (23.9%)		8/46 (17.4%)		7/21 (33.3%)
Hypocalcemia	4/46 (8.7%)		4/46 (8.7%)		1/21 (4.8%)
Hypokalemia	12/46 (26.1%)		20/46 (43.5%)		6/21 (28.6%)
Hypomagnesemia	20/46 (43.5%)		12/46 (26.1%)		11/21 (52.4%)
Hyponatremia	5/46 (10.9%)		10/46 (21.7%)		4/21 (19%)
Musculoskeletal and connective tissue disorders
Arthralgia	2/46 (4.3%)		14/46 (30.4%)		7/21 (33.3%)
Back pain	4/46 (8.7%)		1/46 (2.2%)		1/21 (4.8%)
Generalized muscle weakness	4/46 (8.7%)		2/46 (4.3%)		2/21 (9.5%)
Musculoskeletal and connective tiss disorder - Other	1/46 (2.2%)		0/46 (0%)		3/21 (14.3%)
Myalgia	0/46 (0%)		7/46 (15.2%)		4/21 (19%)
Pain in extremity	0/46 (0%)		9/46 (19.6%)		2/21 (9.5%)
Nervous system disorders
Dizziness	4/46 (8.7%)		6/46 (13%)		2/21 (9.5%)
Dysgeusia	2/46 (4.3%)		4/46 (8.7%)		2/21 (9.5%)
Headache	5/46 (10.9%)		5/46 (10.9%)		1/21 (4.8%)
Peripheral sensory neuropathy	4/46 (8.7%)		9/46 (19.6%)		3/21 (14.3%)
Psychiatric disorders
Anxiety	2/46 (4.3%)		3/46 (6.5%)		1/21 (4.8%)
Depression	1/46 (2.2%)		5/46 (10.9%)		0/21 (0%)
Insomnia	5/46 (10.9%)		4/46 (8.7%)		2/21 (9.5%)
Renal and urinary disorders
Hematuria	2/46 (4.3%)		1/46 (2.2%)		2/21 (9.5%)
Respiratory, thoracic and mediastinal disorders
Cough	2/46 (4.3%)		4/46 (8.7%)		0/21 (0%)
Dyspnea	8/46 (17.4%)		7/46 (15.2%)		4/21 (19%)
Pleural effusion	1/46 (2.2%)		1/46 (2.2%)		2/21 (9.5%)
Skin and subcutaneous tissue disorders
Alopecia	5/46 (10.9%)		15/46 (32.6%)		4/21 (19%)
Dry skin	9/46 (19.6%)		8/46 (17.4%)		3/21 (14.3%)
Palmar-plantar erythrodysesthesia syndrome	1/46 (2.2%)		3/46 (6.5%)		3/21 (14.3%)
Photosensitivity	0/46 (0%)		11/46 (23.9%)		4/21 (19%)
Pruritus	4/46 (8.7%)		4/46 (8.7%)		1/21 (4.8%)
Rash acneiform	27/46 (58.7%)		22/46 (47.8%)		10/21 (47.6%)
Rash maculo-papular	6/46 (13%)		13/46 (28.3%)		2/21 (9.5%)
Skin and subcutaneous tissue disorders - Other	1/46 (2.2%)		8/46 (17.4%)		2/21 (9.5%)
Skin hyperpigmentation	1/46 (2.2%)		1/46 (2.2%)		2/21 (9.5%)
Vascular disorders
Hot flashes	0/46 (0%)		3/46 (6.5%)		1/21 (4.8%)
Hypertension	4/46 (8.7%)		5/46 (10.9%)		1/21 (4.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.