Postoperative Chemotherapy With or Without Bevacizumab for Patients With Stage II or III Rectal Cancer

• Sponsor: ECOG-ACRIN Cancer Research Group (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00303628
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 355
• Locations: 617
• Arms: 2
• Actual Duration (Months): 155.8
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving more than one drug (combination chemotherapy) together with bevacizumab after surgery may kill any tumor cells that remain after surgery. It is not yet known whether oxaliplatin, leucovorin, and fluorouracil is more effective with or without bevacizumab in treating rectal cancer. This randomized phase III trial is studying combination chemotherapy to see how well it works with or without bevacizumab in treating patients who have had surgery for stage II or stage III rectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Rectum; Stage II Rectal Cancer; Stage III Rectal Cancer	Drug: oxaliplatin; Drug: fluorouracil; Drug: leucovorin calcium; Drug: bevacizumab	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. Compare the overall survival of patients who have undergone prior surgery and neoadjuvant chemoradiotherapy for clinical stage II or III rectal cancer treated with adjuvant oxaliplatin, leucovorin calcium, fluorouracil with vs without bevacizumab.

SECONDARY OBJECTIVES:

1. Evaluate tolerance of treatment, patterns of failure, and disease-free survival in patients treated with these regimens

EXPLORATORY OBJECTIVES:

1. Assess long-term rectal function using the Patient Bowel Function/Uniscale questionnaire and the Functional Assessment of Cancer (FACT)-Diarrhea subscale in patients treated with these regimens.

2. Validate the FACT-Diarrhea subscale. III. Assess long-term symptoms of oxaliplatin-related neurotoxicity using the FACT/Gynecologic Oncology Group (GOG)-Neurotoxicity subscale in patients treated with these regimens.

3. Correlate TS, DPD and TP expression (key targets for fluorouracil); retention of chromosome 18q alleles and microsatellite instability (MSI) with TGFβ1RII mutation (markers for fluorouracil efficacy); ERCC1, ERCC2, and XPF expression (participants in repair of adducts from oxaliplatin); and p53 gene mutation and possibly other molecular markers pertinent to vascular endothelial growth factor in tumor tissue specimens with treatment efficacy in these patients.

4. Correlate tumor molecular prognostic markers (chromosome 18q allelic loss and MSI) with survival in patients treated with this regimen.

OUTLINE:

This is a randomized study. Patients are stratified according to Eastern Cooperative Oncology Group (ECOG) performance status (0 vs 1), clinical staging (high risk [T3, N+, M0 or T4, any N, M0] vs low risk [T1-2, N+, M0 or T3, N0, M0]), prior pre-operative oxaliplatin (yes vs no), and prior radiotherapy dose (40-50 Gy vs > 50-55.8 Gy). Patients are randomized to 1 of 2 treatment arms in a 1:1 ratio.

ARM I: Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses* in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive bevacizumab** IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I*.

[Note: *Patients who received prior neoadjuvant oxaliplatin including patients on protocol NSABP-R-04 receive up to 9 courses of treatment followed by leucovorin calcium IV and fluorouracil IV with (arm II) or without (arm I) bevacizumab for up to 3 courses.]

[Note: **Patients no longer receive bevacizumab as of 4/29/2009 when accrual was terminated due to slow accrual for the study)]

Patients complete 10-15 minute questionnaires about bowel function at randomization, end of treatment, 12 months post-treatment and then annually to 5 years post-treatment.

After completion of study treatment, patients are followed periodically for approximately 10 years.

PROJECTED ACCRUAL: 2100 patients

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil and Leucovorin vs Oxaliplatin, 5-Fluorouracil, Leucovorin and Bevacizumab for Patients With Stage II or III Rectal Cancer Receiving Pre-operative Chemoradiation
• Actual Study Start Date: Feb 17, 2006
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: Feb 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses.	Drug: oxaliplatin; Given IV; Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP ; Drug: fluorouracil; Given IV; Other Names: 5-fluorouracil 5-Fluracil 5-FU ; Drug: leucovorin calcium; Given IV; Other Names: CF CFR LV
Experimental: Arm II Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I.	Drug: oxaliplatin; Given IV; Other Names: 1-OHP Dacotin Dacplat Eloxatin L-OHP ; Drug: fluorouracil; Given IV; Other Names: 5-fluorouracil 5-Fluracil 5-FU ; Drug: leucovorin calcium; Given IV; Other Names: CF CFR LV ; Drug: bevacizumab; Given IV; Other Names: anti-VEGF humanized monoclonal antibody anti-VEGF monoclonal antibody Avastin rhuMAb VEGF

Outcome Measures

Primary Outcome Measures

1. 5-year Overall Survival Rate [Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization]

   Overall survival (OS) was defined as time from randomization to date of death from any cause. Patients who were still alive were censored at last date of known alive. Kaplan-Meier method was used to estimate the 5-year OS rate.

Secondary Outcome Measures

1. 5-year Disease-free Survival Rate [Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization]

   Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer or death, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Kaplan-Meier method was used to estimate 5-year DFS rate.

2. Patterns of Failure [Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization]

   Failure included recurrence, second primary cancer and death without recurrence.

3. Proportion of Patients Who Completed 12 Cycles of Treatment [assessed at the end of treatment]

   In the study, treatment was repeated every 2 weeks for a total of 12 cycles on both arms. The total number of cycles of treatment patient received until going off treatment due to any reason was recorded. It was a measure of the tolerance of the therapy.

Other Outcome Measures

1. Change in Rectal Function Between Baseline and 12 Months [assessed at baseline and 12 months after randomization]

   Change in rectal function between baseline and 12 months was measuring the long-term rectal function among the patients. Rectal function was measured using the Bowel Function Questionnaire at baseline and 12 months after randomization. The total score of the questionnaire was calculated as the number of problems with bowel function (score range 0-11). Change in rectal function between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated improved rectal function. This change in score was calculated for each individual patient who had the data.

2. Change in Oxaliplatin-related Neurotoxicity Between Baseline and 12 Months [assessed at baseline and 12 months after randomization]

   Change in oxaliplatin-related neurotoxicity between baseline and 12 months was measuring the long-term symptom of oxaliplatin-related neurotoxicity among the patients. Oxaliplatin-related neurotoxicity was measured using the FACT/GOG-Ntx subscale at baseline and 12 months after randomization. The range of the total score of the scale was between 0 and 44, and lower values indicate higher neurotoxicity. Change in oxaliplatin-related neurotoxicity between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated worsened symptom. This change in score was calculated for each individual patient who had the data.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically confirmed adenocarcinoma of the rectum meeting 1 of the following clinical (e.g., before neoadjuvant therapy) or pathologic staging criteria:

• T3, N+, M0

• T3, N0, M0

• T4, N0, M0

• Any T, N1-2, M0

• T4, N0-2, M0 disease must meet 1 of the following criteria:

• Clinically fixed tumor on rectal examination with tumor adherent to the pelvic sidewall or sacrum

• Hydronephrosis on Computed Tomography (CT) scan or Intravenous Pyelogram (IVP)

• Ureteric or bladder invasion as documented by cystoscopy and cytology or biopsy

• Invasion into prostate

• Vaginal or uterine involvement

• Must have undergone complete tumor resection >= 28 days ago and able to begin treatment by day 56

• Must have undergone concurrent neoadjuvant chemoradiotherapy*

• NOTE: *Neoadjuvant chemoradiotherapy received on protocol NSABP-R-04 allowed provided it met these criteria

• Must have undergone prior radiotherapy at 40-55.8 Gy** AND received 1 of the following chemotherapy regimens:

• Continuous infusion of fluorouracil with or without oxaliplatin; fluorouracil and leucovorin calcium

• Capecitabine with or without oxaliplatin; capecitabine with or without oxaliplatin OR a continuous infusion of fluorouracil with or without oxaliplatin received on protocol NSABP-R-04

• NOTE: **Intensity-modulated radiotherapy allowed

• ECOG performance status 0-1

• Platelet count >= 100,000/mm^3

• Absolute granulocyte count >= 1,500/mm^3

• Bilirubin normal (unless chronic grade 1 bilirubin elevation due to Gilbert's disease or similar syndrome due to slow conjugation of bilirubin)

• Alkaline phosphatase (AP) < 2.5 times upper limit of normal (ULN) and aspartate aminotransferase (AST) < 1.5 times ULN

• Hepatitis B and C negative (for patients with AP > normal) unless previously vaccinated

• Serum creatinine =< 1.5 times ULN

• Urine protein:creatinine (UPC) ratio < 1.0 OR urine protein < 1 g on 24-hour urine collection

• International Normalized Ratio (INR) =< 1.5

• INR > 1.5 allowed provided patient is on full-dose anticoagulants AND meets all of the following criteria:

• In-range INR (i.e., between 2 and 3) on a stable dose of warfarin or low molecular weight heparin

• No active bleeding or pathological condition that is associated with a high risk of bleeding

• Negative pregnancy test

• Fertile patients must use effective contraception during and for at least 3 months after study treatment

• No other previous or concurrent malignancy except nonmelanoma skin cancer, breast cancer in situ, carcinoma in situ of the cervix, or previously treated nonpelvic cancer that has been disease-free for > 5 years

• Patients with a history of breast cancer (without evidence of disease) who remain on hormonal therapy for > 5 years are eligible

• Patients with a history of hypertension must have blood pressure < 150/90 mm Hg AND be on a stable regimen of antihypertensive therapy

• No other prior chemotherapy or pelvic radiotherapy except as neoadjuvant treatment for current diagnosis of rectal cancer

• Concurrent participation on protocol NSABP-R-04 allowed

Exclusion Criteria:

• Pregnant or nursing

• Evidence of metastatic disease on the surgical/intraoperative examination

• Evidence of metastatic disease confirmed by CT scan, Magnetic resonance imaging (MRI), or ultrasound of the liver or chest CT scan or chest x-ray within the past 6 months

• Evidence of tumor outside of the pelvis, including liver metastases, peritoneal seeding, or metastatic inguinal lymphadenopathy

• Concurrent major surgery

• Active bleeding not related to the primary rectal tumor within the past 6 months

• Active inflammatory bowel disease or other serious medical illness which might limit the ability of the patient to receive protocol therapy

• Active gastroduodenal ulcer determined by endoscopy

• Serious or nonhealing wound, skin ulcer, or bone fracture

• Clinically significant peripheral sensory or motor neuropathy >= grade 2

• Nonmalignant systemic disease (e.g., cardiovascular, renal, or hepatic) that would preclude study treatment including, but not limited to, any of the following:

• New York Heart Association class III or IV congestive heart failure

• Concurrent symptomatic arrhythmia

• Transient ischemic attack or cerebrovascular accident

• Arterial thromboembolic event, unstable angina, or myocardial infarction within the past 12 months

• Significant peripheral vascular disease

• Psychiatric or addictive disorders or other conditions that, in the opinion of the investigator, would preclude study requirements

• Significant traumatic injury within the past 28 days

• Known allergy to platinum compounds

• Prior invasive procedure, including either of the following:

• Major surgical procedure or open biopsy within the past 28 days

• Core biopsy or other minor procedure, except placement of a vascular access device, within the past 7 days

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Providence Hospital	Mobile	Alabama	United States	36608
2	Providence Alaska Medical Center	Anchorage	Alaska	United States	99508
3	Mayo Clinic in Arizona	Scottsdale	Arizona	United States	85259
4	Saint Bernards Regional Medical Center	Jonesboro	Arkansas	United States	72401
5	Alta Bates Summit Medical Center-Herrick Campus	Berkeley	California	United States	94704
6	Mills - Peninsula Hospitals	Burlingame	California	United States	94010
7	East Bay Radiation Oncology Center	Castro Valley	California	United States	94546
8	Eden Hospital Medical Center	Castro Valley	California	United States	94546
9	Valley Medical Oncology Consultants-Castro Valley	Castro Valley	California	United States	94546
10	Kaiser Permanente, Fremont	Fremont	California	United States	94538
11	Valley Medical Oncology Consultants-Fremont	Fremont	California	United States	94538
12	Cancer Care Associates of Fresno Medical Group Inc	Fresno	California	United States	93720
13	Saint Jude Medical Center	Fullerton	California	United States	92835
14	Glendale Memorial Hospital and Health Center	Glendale	California	United States	91204
15	Marin General Hospital	Greenbrae	California	United States	94904
16	Kaiser Permanente, Hayward	Hayward	California	United States	94545
17	Saint Rose Hospital	Hayward	California	United States	94545
18	University of Southern California/Norris Cancer Center	Los Angeles	California	United States	90033
19	Contra Costa Regional Medical Center	Martinez	California	United States	94553-3156
20	Fremont - Rideout Cancer Center	Marysville	California	United States	95901
21	Community Hospital of Monterey Peninsula	Monterey	California	United States	93940
22	El Camino Hospital	Mountain View	California	United States	94040
23	Palo Alto Medical Foundation-Camino Division	Mountain View	California	United States	94040
24	Sutter Cancer Research Consortium	Novato	California	United States	94945
25	Highland General Hospital	Oakland	California	United States	94602
26	Alta Bates Summit Medical Center - Summit Campus	Oakland	California	United States	94609
27	Bay Area Breast Surgeons Inc	Oakland	California	United States	94609
28	Bay Area Tumor Institute CCOP	Oakland	California	United States	94609
29	Larry G Strieff MD Medical Corporation	Oakland	California	United States	94609
30	Tom K Lee Inc	Oakland	California	United States	94609
31	Kaiser Permanente-Oakland	Oakland	California	United States	94611
32	Desert Regional Medical Center	Palm Springs	California	United States	92262
33	Palo Alto Medical Foundation Heath Care	Palo Alto	California	United States	94301
34	Valley Care Health System - Pleasanton	Pleasanton	California	United States	94588
35	Valley Medical Oncology Consultants	Pleasanton	California	United States	94588
36	Kaiser Permanente-Redwood City	Redwood City	California	United States	94063
37	Kaiser Permanente-Richmond	Richmond	California	United States	94801
38	Kaiser Permanente-Roseville	Roseville	California	United States	95661
39	University of California at Davis Cancer Center	Sacramento	California	United States	95817
40	Kaiser Permanente-South Sacramento	Sacramento	California	United States	95823
41	Kaiser Permanente - Sacramento	Sacramento	California	United States	95825
42	Salinas Valley Memorial	Salinas	California	United States	93901
43	University of California At San Diego	San Diego	California	United States	92103
44	Kaiser Permanente	San Diego	California	United States	92120
45	Kaiser Permanente-San Francisco	San Francisco	California	United States	94115
46	California Pacific Medical Center	San Francisco	California	United States	94118
47	Kaiser Permanente-Santa Teresa-San Jose	San Jose	California	United States	95119
48	Doctors Medical Center- JC Robinson Regional Cancer Center	San Pablo	California	United States	94806
49	Kaiser Permanente-San Rafael	San Rafael	California	United States	94903
50	Kaiser Permanente Medical Center - Santa Clara	Santa Clara	California	United States	95051
51	Kaiser Permanente-Santa Rosa	Santa Rosa	California	United States	95403
52	Kaiser Permanente-South San Francisco	South San Francisco	California	United States	94080
53	Kaiser Permanente-Stockton	Stockton	California	United States	95210
54	Tahoe Forest Cancer Center	Truckee	California	United States	96161
55	Kaiser Permanente-Vallejo	Vallejo	California	United States	94589
56	Sutter Solano Medical Center	Vallejo	California	United States	94589
57	Kaiser Permanente-Walnut Creek	Walnut Creek	California	United States	94596
58	The Medical Center of Aurora	Aurora	Colorado	United States	80012
59	Boulder Community Hospital	Boulder	Colorado	United States	80301
60	Penrose-Saint Francis Healthcare	Colorado Springs	Colorado	United States	80907
61	Memorial Hospital Colorado Springs	Colorado Springs	Colorado	United States	80909
62	Porter Adventist Hospital	Denver	Colorado	United States	80210
63	Exempla Saint Joseph Hospital	Denver	Colorado	United States	80218
64	Presbyterian - Saint Lukes Medical Center - Health One	Denver	Colorado	United States	80218
65	Rose Medical Center	Denver	Colorado	United States	80220
66	Colorado Cancer Research Program CCOP	Denver	Colorado	United States	80224-2522
67	Swedish Medical Center	Englewood	Colorado	United States	80113
68	Front Range Cancer Specialists	Fort Collins	Colorado	United States	80528
69	Saint Mary's Hospital and Regional Medical Center	Grand Junction	Colorado	United States	81502
70	North Colorado Medical Center	Greeley	Colorado	United States	80631
71	Saint Anthony Hospital	Lakewood	Colorado	United States	80228
72	Sky Ridge Medical Center	Lone Tree	Colorado	United States	80124
73	Longmont United Hospital	Longmont	Colorado	United States	80501
74	McKee Medical Center	Loveland	Colorado	United States	80539
75	Saint Mary Corwin Medical Center	Pueblo	Colorado	United States	81004
76	North Suburban Medical Center	Thornton	Colorado	United States	80229
77	Exempla Lutheran Medical Center	Wheat Ridge	Colorado	United States	80033
78	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut	United States	06360
79	Beebe Medical Center	Lewes	Delaware	United States	19958
80	Christiana Care Health System-Christiana Hospital	Newark	Delaware	United States	19718
81	Washington Hospital Center	Washington	District of Columbia	United States	20010
82	Lombardi Comprehensive Cancer Center at Georgetown University	Washington	District of Columbia	United States	20057
83	Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
84	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224-9980
85	Jupiter Medical Center	Jupiter	Florida	United States	33458
86	The Watson Clinic	Lakeland	Florida	United States	33805
87	Mount Sinai Medical Center CCOP	Miami Beach	Florida	United States	33140
88	University of Miami Miller School of Medicine-Sylvester Cancer Center	Miami	Florida	United States	33136
89	Cancer Specialists of North Florida-Orange Park	Orange Park	Florida	United States	32073
90	University Cancer and Blood Center LLC	Athens	Georgia	United States	30607
91	Piedmont Hospital	Atlanta	Georgia	United States	30309
92	Atlanta Regional CCOP	Atlanta	Georgia	United States	30342
93	Northside Hospital	Atlanta	Georgia	United States	30342
94	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia	United States	30342
95	Georgia Regents University	Augusta	Georgia	United States	30912
96	Well Star Cobb Hospital	Austell	Georgia	United States	30106
97	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
98	Dekalb Medical Center	Decatur	Georgia	United States	30033
99	Gwinnett Medical Center	Lawrenceville	Georgia	United States	30045
100	Medical Center of Central Georgia	Macon	Georgia	United States	31208
101	Wellstar Kennestone Hospital	Marietta	Georgia	United States	30060
102	Southern Regional Medical Center	Riverdale	Georgia	United States	30274
103	Harbin Clinic Medical Oncology and Clinical Research	Rome	Georgia	United States	30165
104	Memorial Health University Medical Center	Savannah	Georgia	United States	31403
105	Pali Momi Medical Center	'Aiea	Hawaii	United States	96701
106	Oncare Hawaii Inc-POB II	Honolulu	Hawaii	United States	96813
107	Queen's Medical Center	Honolulu	Hawaii	United States	96813
108	Straub Clinic and Hospital	Honolulu	Hawaii	United States	96813
109	University of Hawaii	Honolulu	Hawaii	United States	96813
110	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii	United States	96817
111	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii	United States	96817
112	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826
113	Tripler Army Medical Center	Honolulu	Hawaii	United States	96859
114	Maui Memorial Medical Center	Wailuku	Hawaii	United States	96793
115	Pacific Cancer Institute of Maui	Wailuku	Hawaii	United States	96793
116	Saint Alphonsus Regional Medical Center	Boise	Idaho	United States	83706
117	Saint Luke's Mountain States Tumor Institute	Boise	Idaho	United States	83712
118	Hematology Oncology Associates of Eastern Idaho	Idaho Falls	Idaho	United States	83404
119	Portneuf Medical Center	Pocatello	Idaho	United States	83201
120	Saint Anthony's Health	Alton	Illinois	United States	62002
121	Rush - Copley Medical Center	Aurora	Illinois	United States	60504
122	Saint Joseph Medical Center	Bloomington	Illinois	United States	61701
123	Graham Hospital Association	Canton	Illinois	United States	61520
124	Memorial Hospital	Carthage	Illinois	United States	62321
125	Mount Sinai Hospital Medical Center	Chicago	Illinois	United States	60608
126	Hematology and Oncology Associates	Chicago	Illinois	United States	60611
127	Northwestern University	Chicago	Illinois	United States	60611
128	John H Stroger Jr Hospital of Cook County	Chicago	Illinois	United States	60612-3785
129	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois	United States	60612
130	Rush University Medical Center	Chicago	Illinois	United States	60612
131	Mercy Hospital and Medical Center	Chicago	Illinois	United States	60616
132	Swedish Covenant Hospital	Chicago	Illinois	United States	60625
133	Resurrection Healthcare	Chicago	Illinois	United States	60631
134	University of Chicago	Chicago	Illinois	United States	60637
135	Decatur Memorial Hospital	Decatur	Illinois	United States	62526
136	Good Samaritan Hospital	Downers Grove	Illinois	United States	60515
137	Elmhurst Memorial Hospital	Elmhurst	Illinois	United States	60126
138	Eureka Hospital	Eureka	Illinois	United States	61530
139	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois	United States	60201
140	Saint Francis Hospital	Evanston	Illinois	United States	60202
141	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
142	Illinois CancerCare Galesburg	Galesburg	Illinois	United States	61401
143	Western Illinois Cancer Treatment Center	Galesburg	Illinois	United States	61401
144	Mason District Hospital	Havana	Illinois	United States	62644
145	Hinsdale Hematology Oncology Associates Incorporated	Hinsdale	Illinois	United States	60521
146	Hopedale Medical Complex - Hospital	Hopedale	Illinois	United States	61747
147	Midwest Center for Hematology Oncology	Joliet	Illinois	United States	60432
148	Joliet Oncology-Hematology Associates Limited	Joliet	Illinois	United States	60435
149	Kewanee Hospital	Kewanee	Illinois	United States	61443
150	North Shore Hematology Oncology	Libertyville	Illinois	United States	60048
151	Mcdonough District Hospital	Macomb	Illinois	United States	61455
152	Loyola University Medical Center	Maywood	Illinois	United States	60153
153	Garneau, Stewart C MD (UIA Investigator)	Moline	Illinois	United States	61265
154	Porubcin, Michael MD (UIA Investigator)	Moline	Illinois	United States	61265
155	Sharis, Christine M MD (UIA Investigator)	Moline	Illinois	United States	61265
156	Stoffel, Thomas J MD (UIA Investigator)	Moline	Illinois	United States	61265
157	Vigliotti, Antonio, P.G. M.D. (UIA Investigator)	Moline	Illinois	United States	61265
158	Good Samaritan Regional Health Center	Mount Vernon	Illinois	United States	62864
159	Edward Hospital/Cancer Center	Naperville	Illinois	United States	60540
160	Illinois Cancer Specialists-Niles	Niles	Illinois	United States	60714
161	Bromenn Regional Medical Center	Normal	Illinois	United States	61761
162	Community Cancer Center Foundation	Normal	Illinois	United States	61761
163	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois	United States	61350
164	Ottawa Regional Hospital and Healthcare Center	Ottawa	Illinois	United States	61350
165	Pekin Cancer Treatment Center	Pekin	Illinois	United States	61554
166	Pekin Hospital	Pekin	Illinois	United States	61554
167	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61603
168	Proctor Hospital	Peoria	Illinois	United States	61614
169	OSF Saint Francis Medical Center Radiation Oncology Service at the Central Illinois Comprehensive CC	Peoria	Illinois	United States	61615-7827
170	Illinois CancerCare-Peoria	Peoria	Illinois	United States	61615
171	Illinois Oncology Research Association CCOP	Peoria	Illinois	United States	61615
172	OSF Saint Francis Medical Center	Peoria	Illinois	United States	61637
173	Illinois Valley Hospital	Peru	Illinois	United States	61354
174	Valley Radiation Oncology	Peru	Illinois	United States	61354
175	Perry Memorial Hospital	Princeton	Illinois	United States	61356
176	Swedish American Hospital	Rockford	Illinois	United States	61104
177	Edward H Kaplan MD and Associates	Skokie	Illinois	United States	60076
178	Hematology Oncology Associates of Illinois - Skokie	Skokie	Illinois	United States	60076
179	Midwest Cancer Research Group Incorporated	Skokie	Illinois	United States	60077
180	Saint Margaret's Hospital	Spring Valley	Illinois	United States	61362
181	Memorial Medical Center	Springfield	Illinois	United States	62781-0001
182	Carle Cancer Center	Urbana	Illinois	United States	61801
183	Carle Clinic-Urbana Main	Urbana	Illinois	United States	61801
184	Saint Francis Hospital and Health Centers	Beech Grove	Indiana	United States	46107
185	Elkhart General Hospital	Elkhart	Indiana	United States	46515
186	Fort Wayne Medical Oncology and Hematology Inc-Parkview	Fort Wayne	Indiana	United States	46845
187	Saint Vincent Hospital and Health Services	Indianapolis	Indiana	United States	46260
188	Community Howard Regional Health	Kokomo	Indiana	United States	46904
189	IU Health La Porte Hospital	La Porte	Indiana	United States	46350
190	Franciscan Saint Anthony Health-Michigan City	Michigan City	Indiana	United States	46360
191	Saint Joseph Regional Medical Center-Mishawaka	Mishawaka	Indiana	United States	46545-1470
192	IU Health Ball Memorial Hospital	Muncie	Indiana	United States	47303
193	Oncology Hematology Associates of Southwest Indiana	Newburgh	Indiana	United States	47630
194	Reid Hospital and Health Care Services	Richmond	Indiana	United States	47374
195	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
196	Northern Indiana Cancer Research Consortium	South Bend	Indiana	United States	46628
197	McFarland Clinic PC-William R Bliss Cancer Center	Ames	Iowa	United States	50010
198	Constantinou, Costas L MD (UIA Investigator)	Bettendorf	Iowa	United States	52722
199	Cedar Rapids Oncology Association	Cedar Rapids	Iowa	United States	52403
200	Oncology Associates at Mercy Medical Center	Cedar Rapids	Iowa	United States	52403
201	Medical Oncology and Hematology Associates-West Des Moines	Clive	Iowa	United States	50325
202	Genesis Medical Center - East Campus	Davenport	Iowa	United States	52803
203	Genesis Medical Center - West Campus	Davenport	Iowa	United States	52804
204	Mercy Capitol	Des Moines	Iowa	United States	50307
205	Iowa Methodist Medical Center	Des Moines	Iowa	United States	50309
206	Iowa Oncology Research Association CCOP	Des Moines	Iowa	United States	50309
207	Medical Oncology and Hematology Associates-Des Moines	Des Moines	Iowa	United States	50309
208	Medical Oncology and Hematology Associates-Laurel	Des Moines	Iowa	United States	50314
209	Mercy Medical Center - Des Moines	Des Moines	Iowa	United States	50314
210	Iowa Lutheran Hospital	Des Moines	Iowa	United States	50316
211	University of Iowa Hospitals and Clinics	Iowa City	Iowa	United States	52242
212	Mercy Medical Center - North Iowa	Mason City	Iowa	United States	50401
213	Siouxland Regional Cancer Center	Sioux City	Iowa	United States	51101-1733
214	Siouxland Hematology Oncology Associates	Sioux City	Iowa	United States	51101
215	Mercy Medical Center-Sioux City	Sioux City	Iowa	United States	51104
216	Saint Luke's Regional Medical Center	Sioux City	Iowa	United States	51104
217	Cedar Valley Medical Specialists	Waterloo	Iowa	United States	50701
218	Covenant Medical Center	Waterloo	Iowa	United States	50702
219	Hospital District Sixth of Harper County	Anthony	Kansas	United States	67003
220	Cancer Center of Kansas - Chanute	Chanute	Kansas	United States	66720
221	Cancer Center of Kansas - Dodge City	Dodge City	Kansas	United States	67801
222	Cancer Center of Kansas - El Dorado	El Dorado	Kansas	United States	67042
223	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas	United States	66701
224	Cancer Center of Kansas-Independence	Independence	Kansas	United States	67301
225	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
226	Cancer Center of Kansas-Kingman	Kingman	Kansas	United States	67068
227	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
228	Cancer Center of Kansas - Newton	Newton	Kansas	United States	67114
229	Olathe Cancer Center	Olathe	Kansas	United States	66061
230	Cancer Center of Kansas - Parsons	Parsons	Kansas	United States	67357
231	Cancer Center of Kansas - Pratt	Pratt	Kansas	United States	67124
232	Cancer Center of Kansas - Salina	Salina	Kansas	United States	67401
233	Stormont-Vail Regional Health Center	Topeka	Kansas	United States	66604
234	Cancer Center of Kansas - Wellington	Wellington	Kansas	United States	67152
235	Associates In Womens Health	Wichita	Kansas	United States	67208
236	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
237	Cancer Center of Kansas - Main Office	Wichita	Kansas	United States	67214
238	Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
239	Wichita CCOP	Wichita	Kansas	United States	67214
240	Cancer Center of Kansas - Winfield	Winfield	Kansas	United States	67156
241	The James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky	United States	40202
242	Eastern Maine Medical Center	Bangor	Maine	United States	04401
243	Saint Mary's Regional Medical Center	Lewiston	Maine	United States	04240
244	Maine Medical Center- Scarborough Campus	Scarborough	Maine	United States	04074
245	Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
246	Memorial Hospital at Easton - Shore Regional Cancer Center	Easton	Maryland	United States	21601
247	Union Hospital of Cecil County	Elkton	Maryland	United States	21921
248	Eastern Cooperative Oncology Group	Boston	Massachusetts	United States	02215
249	Caritas Saint Elizabeth's Medical Center	Brighton	Massachusetts	United States	02135-2997
250	Lahey Hospital and Medical Center	Burlington	Massachusetts	United States	01805
251	Simonds-Sinon Regional Cancer Center	Fitchburg	Massachusetts	United States	01420
252	Berkshire Hematology Oncology PC	Pittsfield	Massachusetts	United States	01201
253	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
254	Bixby Medical Center	Adrian	Michigan	United States	49221
255	Hickman Cancer Center	Adrian	Michigan	United States	49221
256	Saint Joseph Mercy Hospital	Ann Arbor	Michigan	United States	48106-0995
257	Michigan Cancer Research Consortium Community Clinical Oncology Program	Ann Arbor	Michigan	United States	48106
258	Bronson Battle Creek	Battle Creek	Michigan	United States	49017
259	Spectrum Health Big Rapids Hospital	Big Rapids	Michigan	United States	49307
260	Oakwood Hospital	Dearborn	Michigan	United States	48124
261	Wayne State University/Karmanos Cancer Institute	Detroit	Michigan	United States	48201
262	Saint John Hospital and Medical Center	Detroit	Michigan	United States	48236
263	Green Bay Oncology - Escanaba	Escanaba	Michigan	United States	49431
264	Hurley Medical Center	Flint	Michigan	United States	48502
265	Genesys Regional Medical Center-West Flint Campus	Flint	Michigan	United States	48532
266	Grand Rapids Clinical Oncology Program	Grand Rapids	Michigan	United States	49503
267	Mercy Health Saint Mary's	Grand Rapids	Michigan	United States	49503
268	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
269	Holland Community Hospital	Holland	Michigan	United States	49423
270	Green Bay Oncology - Iron Mountain	Iron Mountain	Michigan	United States	49801
271	Allegiance Health	Jackson	Michigan	United States	49201
272	Sparrow Hospital	Lansing	Michigan	United States	48912
273	Saint Mary Mercy Hospital	Livonia	Michigan	United States	48154
274	Marquette General Hospital	Marquette	Michigan	United States	49855
275	Community Cancer Center of Monroe	Monroe	Michigan	United States	48162
276	Mercy Memorial Hospital	Monroe	Michigan	United States	48162
277	Mercy Health Partners-Hackley Campus	Muskegon	Michigan	United States	49442
278	Mercy Health Mercy Campus	Muskegon	Michigan	United States	49444
279	Saint Joseph Mercy Oakland	Pontiac	Michigan	United States	48341-2985
280	Saint Joseph Mercy Port Huron	Port Huron	Michigan	United States	48060
281	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
282	Saint Mary's of Michigan	Saginaw	Michigan	United States	48601
283	Lakeland Hospital	Saint Joseph	Michigan	United States	49085
284	Munson Medical Center	Traverse City	Michigan	United States	49684
285	Saint John Macomb-Oakland Hospital	Warren	Michigan	United States	48093
286	Metro Health Hospital	Wyoming	Michigan	United States	49519
287	Sanford Clinic North-Bemidgi	Bemidji	Minnesota	United States	56601
288	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
289	Mercy Hospital	Coon Rapids	Minnesota	United States	55433
290	Essentia Health Duluth Clinic CCOP	Duluth	Minnesota	United States	55805
291	Essentia Health Saint Mary's Medical Center	Duluth	Minnesota	United States	55805
292	Miller-Dwan Hospital	Duluth	Minnesota	United States	55805
293	Fairview-Southdale Hospital	Edina	Minnesota	United States	55435
294	Unity Hospital	Fridley	Minnesota	United States	55432
295	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
296	Meeker County Memorial Hospital	Litchfield	Minnesota	United States	55355
297	Mayo Clinic Health Systems-Mankato	Mankato	Minnesota	United States	56001
298	Minnesota Oncology Hematology PA-Maplewood	Maplewood	Minnesota	United States	55109
299	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
300	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
301	Virginia Piper Cancer Institute	Minneapolis	Minnesota	United States	55407
302	Hennepin County Medical Center	Minneapolis	Minnesota	United States	55415
303	Minneapolis Veterans Medical Center	Minneapolis	Minnesota	United States	55417
304	North Memorial Medical Health Center	Robbinsdale	Minnesota	United States	55422
305	Mayo Clinic	Rochester	Minnesota	United States	55905
306	Metro-Minnesota CCOP	Saint Louis Park	Minnesota	United States	55416
307	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
308	Regions Hospital	Saint Paul	Minnesota	United States	55101
309	Saint Joseph's Hospital - Healtheast	Saint Paul	Minnesota	United States	55102
310	United Hospital	Saint Paul	Minnesota	United States	55102
311	Saint Francis Regional Medical Center	Shakopee	Minnesota	United States	55379
312	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
313	Rice Memorial Hospital	Willmar	Minnesota	United States	56201
314	Minnesota Oncology and Hematology PA-Woodbury	Woodbury	Minnesota	United States	55125
315	Woodwinds Health Campus	Woodbury	Minnesota	United States	55125
316	Southeast Missouri Hospital	Cape Girardeau	Missouri	United States	63701
317	Saint Francis Medical Center	Cape Girardeau	Missouri	United States	63703
318	Freeman Health System	Joplin	Missouri	United States	64804
319	Mercy Hospital-Joplin	Joplin	Missouri	United States	64804
320	Saint Louis Cancer and Breast Institute-South City	Saint Louis	Missouri	United States	63109
321	Saint Louis University Hospital	Saint Louis	Missouri	United States	63110
322	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
323	Missouri Baptist Medical Center	Saint Louis	Missouri	United States	63131
324	Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
325	Saint John's Mercy Medical Center	Saint Louis	Missouri	United States	63141
326	Saint Louis-Cape Girardeau CCOP	Saint Louis	Missouri	United States	63141
327	Mercy Hospital Springfield	Springfield	Missouri	United States	65804
328	CoxHealth South Hospital	Springfield	Missouri	United States	65807
329	Montana Cancer Consortium CCOP	Billings	Montana	United States	59101
330	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
331	Saint Vincent Healthcare	Billings	Montana	United States	59101
332	Hematology-Oncology Centers of the Northern Rockies PC	Billings	Montana	United States	59102
333	Billings Clinic	Billings	Montana	United States	59107-7000
334	Deaconess Medical Center	Billings	Montana	United States	59107
335	Bozeman Deaconess Cancer Center	Bozeman	Montana	United States	59715
336	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
337	Saint James Community Hospital and Cancer Treatment Center	Butte	Montana	United States	59701
338	Benefis Healthcare- Sletten Cancer Institute	Great Falls	Montana	United States	59405
339	Berdeaux, Donald MD (UIA Investigator)	Great Falls	Montana	United States	59405
340	Great Falls Clinic	Great Falls	Montana	United States	59405
341	Northern Montana Hospital	Havre	Montana	United States	59501
342	Saint Peter's Community Hospital	Helena	Montana	United States	59601
343	Glacier Oncology PLLC	Kalispell	Montana	United States	59901
344	Kalispell Medical Oncology	Kalispell	Montana	United States	59901
345	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
346	Community Medical Hospital	Missoula	Montana	United States	59801
347	Montana Cancer Specialists	Missoula	Montana	United States	59802
348	Saint Patrick Hospital - Community Hospital	Missoula	Montana	United States	59802
349	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
350	Nebraska Cancer Research Center	Lincoln	Nebraska	United States	68510
351	Missouri Valley Cancer Consortium CCOP	Omaha	Nebraska	United States	68106
352	Nebraska Methodist Hospital	Omaha	Nebraska	United States	68114
353	Alegent Health Immanuel Medical Center	Omaha	Nebraska	United States	68122
354	Alegent Health Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
355	Creighton University Medical Center	Omaha	Nebraska	United States	68131
356	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198
357	University Medical Center of Southern Nevada	Las Vegas	Nevada	United States	89102
358	Nevada Cancer Research Foundation CCOP	Las Vegas	Nevada	United States	89106
359	Exeter Hospital	Exeter	New Hampshire	United States	03833
360	Cheshire Medical Center-Dartmouth-Hitchcock Keene	Keene	New Hampshire	United States	03431
361	Elliot Hospital	Manchester	New Hampshire	United States	03103
362	Ocean Medical Center	Brick	New Jersey	United States	08724
363	Cooper Hospital University Medical Center	Camden	New Jersey	United States	08103
364	Cancer Institute of New Jersey At Hamilton	Hamilton	New Jersey	United States	08690
365	Monmouth Medical Center	Long Branch	New Jersey	United States	07740
366	Mountainside Hospital	Montclair	New Jersey	United States	07042
367	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962
368	Fox Chase Cancer Center at Virtua Memorial Hospital of Burlington County	Mount Holly	New Jersey	United States	08060
369	Rutgers Cancer Institute of New Jersey	New Brunswick	New Jersey	United States	08903
370	Newark Beth Israel Medical Center	Newark	New Jersey	United States	07112
371	Valley Hospital	Ridgewood	New Jersey	United States	07450
372	Sparta Cancer Treatment Center	Sparta	New Jersey	United States	07871
373	Overlook Hospital	Summit	New Jersey	United States	07902
374	Virtua West Jersey Hospital Voorhees	Voorhees	New Jersey	United States	08043
375	Hematology Oncology Associates	Albuquerque	New Mexico	United States	87106
376	University of New Mexico Cancer Center	Albuquerque	New Mexico	United States	87106
377	Presbyterian Kaseman Hospital	Albuquerque	New Mexico	United States	87110
378	New Mexico Cancer Care Associates	Santa Fe	New Mexico	United States	87505
379	Albert Einstein College of Medicine	Bronx	New York	United States	10461
380	Montefiore Medical Center	Bronx	New York	United States	10467-2490
381	Kings County Hospital	Brooklyn	New York	United States	11203
382	State University of New York Downstate Medical Center	Brooklyn	New York	United States	11203
383	University Hospital of Brooklyn	Brooklyn	New York	United States	11203
384	Veterans Affairs Western New York Health Care System-Buffalo	Buffalo	New York	United States	14215
385	Roswell Park Cancer Institute	Buffalo	New York	United States	14263
386	Hematology Oncology Associates of Central New York PC-East Syracuse	East Syracuse	New York	United States	13057
387	Glens Falls Hospital	Glens Falls	New York	United States	12801
388	Orange Regional Medical Center	Middletown	New York	United States	10940
389	New York University Langone Medical Center	New York	New York	United States	10016
390	Columbia University Medical Center	New York	New York	United States	10032
391	Weill Medical College of Cornell University	New York	New York	United States	10065
392	Highland Hospital	Rochester	New York	United States	14620
393	Interlakes Foundation Inc-Rochester	Rochester	New York	United States	14623
394	University of Rochester	Rochester	New York	United States	14642
395	State University of New York Upstate Medical University	Syracuse	New York	United States	13210
396	Community General Hospital	Syracuse	New York	United States	13215
397	Mission Hospital-Memorial Campus	Asheville	North Carolina	United States	28801
398	Cone Health Alamance Regional Medical Center	Burlington	North Carolina	United States	27216
399	Carolinas Medical Center	Charlotte	North Carolina	United States	28203
400	Carolinas Medical Center - Northeast	Concord	North Carolina	United States	28025
401	Wayne Memorial Hospital	Goldsboro	North Carolina	United States	27534
402	Wayne Radiation Oncology	Goldsboro	North Carolina	United States	27534
403	Rutherford Hospital	Rutherfordton	North Carolina	United States	28139
404	Wilson Medical Center	Wilson	North Carolina	United States	27893
405	Bismarck Cancer Center	Bismarck	North Dakota	United States	58501
406	Mid Dakota Clinic	Bismarck	North Dakota	United States	58501
407	Saint Alexius Medical Center	Bismarck	North Dakota	United States	58501
408	Sanford Bismarck Medical Center	Bismarck	North Dakota	United States	58501
409	Sanford Clinic North-Fargo	Fargo	North Dakota	United States	58122
410	Sanford Medical Center-Fargo	Fargo	North Dakota	United States	58122
411	Altru Cancer Center	Grand Forks	North Dakota	United States	58201
412	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
413	Toledo Clinic Cancer Centers-Bowling Green	Bowling Green	Ohio	United States	43402
414	Mercy Medical Center	Canton	Ohio	United States	44708
415	Aultman Health Foundation	Canton	Ohio	United States	44710
416	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
417	The Christ Hospital	Cincinnati	Ohio	United States	45219
418	University of Cincinnati	Cincinnati	Ohio	United States	45267
419	Case Western Reserve University	Cleveland	Ohio	United States	44106
420	MetroHealth Medical Center	Cleveland	Ohio	United States	44109
421	Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
422	North Coast Cancer Care-Clyde	Clyde	Ohio	United States	43410
423	Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Columbus	Ohio	United States	43210
424	Riverside Methodist Hospital	Columbus	Ohio	United States	43214
425	Columbus CCOP	Columbus	Ohio	United States	43215
426	Grant Medical Center	Columbus	Ohio	United States	43215
427	Mount Carmel Health Center West	Columbus	Ohio	United States	43222
428	Doctors Hospital	Columbus	Ohio	United States	43228
429	Grandview Hospital	Dayton	Ohio	United States	45405
430	Good Samaritan Hospital - Dayton	Dayton	Ohio	United States	45406
431	Miami Valley Hospital	Dayton	Ohio	United States	45409
432	Samaritan North Health Center	Dayton	Ohio	United States	45415
433	Dayton CCOP	Dayton	Ohio	United States	45420
434	Veteran Affairs Medical Center	Dayton	Ohio	United States	45428
435	Grady Memorial Hospital	Delaware	Ohio	United States	43015
436	Hematology Oncology Center Incorporated	Elyria	Ohio	United States	44035
437	Blanchard Valley Hospital	Findlay	Ohio	United States	45840
438	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
439	Fremont Memorial Hospital	Fremont	Ohio	United States	43420
440	Wayne Hospital	Greenville	Ohio	United States	45331
441	Cleveland Clinic Cancer Center Independence	Independence	Ohio	United States	44131
442	Cole, Sharon, K. M.D. (UIA Investigator)	Kenton	Ohio	United States	43326
443	Kettering Medical Center	Kettering	Ohio	United States	45429
444	Fairfield Medical Center	Lancaster	Ohio	United States	43130
445	Lima Memorial Hospital	Lima	Ohio	United States	45804
446	Marietta Memorial Hospital	Marietta	Ohio	United States	45750
447	Saint Luke's Hospital	Maumee	Ohio	United States	43537
448	Toledo Clinic Cancer Centers-Maumee	Maumee	Ohio	United States	43537
449	Toledo Radiation Oncology at Northwest Ohio Onocolgy Center	Maumee	Ohio	United States	43537
450	Licking Memorial Hospital	Newark	Ohio	United States	43055
451	Saint Charles Hospital	Oregon	Ohio	United States	43616
452	Toledo Clinic Cancer Centers-Oregon	Oregon	Ohio	United States	43616
453	Firelands Regional Medical Center	Sandusky	Ohio	United States	44870
454	North Coast Cancer Care	Sandusky	Ohio	United States	44870
455	Springfield Regional Medical Center	Springfield	Ohio	United States	45505
456	Flower Hospital	Sylvania	Ohio	United States	43560
457	Mercy Hospital of Tiffin	Tiffin	Ohio	United States	44883
458	The Toledo Hospital/Toledo Children's Hospital	Toledo	Ohio	United States	43606
459	Saint Vincent Mercy Medical Center	Toledo	Ohio	United States	43608
460	University of Toledo	Toledo	Ohio	United States	43614
461	Toledo Community Hospital Oncology Program CCOP	Toledo	Ohio	United States	43617
462	Mercy Saint Anne Hospital	Toledo	Ohio	United States	43623
463	Stark, Michael, Edward. M.D. (UIA Investigator)	Toledo	Ohio	United States	43623
464	Toledo Clinic Cancer Centers-Toledo	Toledo	Ohio	United States	43623
465	Upper Valley Medical Center	Troy	Ohio	United States	45373
466	Fulton County Health Center	Wauseon	Ohio	United States	43567
467	Saint Ann's Hospital	Westerville	Ohio	United States	43081
468	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
469	Cleveland Clinic Wooster Specialty Center	Wooster	Ohio	United States	44691
470	Greene Memorial Hospital	Xenia	Ohio	United States	45385
471	Genesis HealthCare System	Zanesville	Ohio	United States	43701
472	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
473	Cancer Care Associates	Oklahoma City	Oklahoma	United States	73120
474	Natalie Warren Bryant Cancer Center at Saint Francis	Tulsa	Oklahoma	United States	74136
475	Saint Charles Medical Center-Bend	Bend	Oregon	United States	97701
476	Providence Milwaukie Hospital	Milwaukie	Oregon	United States	97222
477	Providence Portland Medical Center	Portland	Oregon	United States	97213
478	Western Oncology Research Consortium	Portland	Oregon	United States	97213
479	Adventist Medical Center	Portland	Oregon	United States	97216
480	Providence Saint Vincent Medical Center	Portland	Oregon	United States	97225
481	Kaiser Permanente	Portland	Oregon	United States	97227
482	Abington Memorial Hospital	Abington	Pennsylvania	United States	19001
483	Lehigh Valley Hospital	Allentown	Pennsylvania	United States	18105
484	Saint Luke's University Hospital-Bethlehem Campus	Bethlehem	Pennsylvania	United States	18015
485	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
486	Geisinger Medical Center	Danville	Pennsylvania	United States	17822-2001
487	Armstrong Center for Medicine and Health	Kittanning	Pennsylvania	United States	16201
488	Riddle Hospital	Media	Pennsylvania	United States	19063
489	Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301
490	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
491	Pennsylvania Hospital	Philadelphia	Pennsylvania	United States	19107
492	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
493	Fox Chase Cancer Center	Philadelphia	Pennsylvania	United States	19111
494	Albert Einstein Medical Center	Philadelphia	Pennsylvania	United States	19141
495	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
496	University of Pittsburgh	Pittsburgh	Pennsylvania	United States	15232
497	Pottstown Memorial Medical Center	Pottstown	Pennsylvania	United States	19464
498	Mercy Hospital	Scranton	Pennsylvania	United States	18501
499	Hematology and Oncology Associates of North East Pennsylvania	Scranton	Pennsylvania	United States	18508
500	Scranton Hematology Oncology	Scranton	Pennsylvania	United States	18510
501	Geisinger Medical Group	State College	Pennsylvania	United States	16801
502	Reading Hospital	West Reading	Pennsylvania	United States	19611
503	Geisinger Wyoming Valley	Wilkes-Barre	Pennsylvania	United States	18711
504	Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
505	Mainline Health CCOP	Wynnewood	Pennsylvania	United States	19096
506	WellSpan Health-York Hospital	York	Pennsylvania	United States	17405
507	Hematology and Oncology Associates of Rhode Island Inc	Cranston	Rhode Island	United States	02920
508	Kent County Hospital	Warwick	Rhode Island	United States	02886
509	AnMed Health Hospital	Anderson	South Carolina	United States	29621
510	Roper Hospital	Charleston	South Carolina	United States	29401
511	McLeod Regional Medical Center	Florence	South Carolina	United States	29506
512	Greenville Health System Cancer Institute/Greenville CCOP	Greenville	South Carolina	United States	29615
513	Spartanburg Regional Medical Center	Spartanburg	South Carolina	United States	29303
514	Upstate Carolina CCOP	Spartanburg	South Carolina	United States	29303
515	Sanford Cancer Center-Oncology Clinic	Sioux Falls	South Dakota	United States	57104
516	Medical X-Ray Center	Sioux Falls	South Dakota	United States	57105
517	Sanford USD Medical Center - Sioux Falls	Sioux Falls	South Dakota	United States	57117-5134
518	Wellmont Holston Valley Hospital and Medical Center	Kingsport	Tennessee	United States	37660
519	Thompson Cancer Survival Center	Knoxville	Tennessee	United States	37916
520	University of Tennessee - Memphis	Memphis	Tennessee	United States	38163
521	Nashville Oncology Associates PC	Nashville	Tennessee	United States	37203
522	Tennessee Oncology PLLC- Centennial Medical Center	Nashville	Tennessee	United States	37203
523	Meharry Medical College	Nashville	Tennessee	United States	37208-3599
524	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37232
525	Parkland Memorial Hospital	Dallas	Texas	United States	75235
526	Zale Lipshy University Hospital	Dallas	Texas	United States	75235
527	Saint Paul Hospital	Dallas	Texas	United States	75390
528	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390
529	Texas Tech University Health Sciences Center	Lubbock	Texas	United States	79430
530	Scott and White Memorial Hospital	Temple	Texas	United States	76508
531	American Fork Hospital	American Fork	Utah	United States	84003
532	Sandra L Maxwell Cancer Center	Cedar City	Utah	United States	84720
533	Logan Regional Hospital	Logan	Utah	United States	84321
534	Cottonwood Hospital Medical Center	Murray	Utah	United States	84107
535	Intermountain Medical Center	Murray	Utah	United States	84157
536	McKay-Dee Hospital Center	Ogden	Utah	United States	84403
537	Utah Valley Regional Medical Center	Provo	Utah	United States	84604-3337
538	Dixie Medical Center Regional Cancer Center	Saint George	Utah	United States	84770
539	Intermountain Health Care	Salt Lake City	Utah	United States	84103
540	Utah Cancer Specialists-Salt Lake City	Salt Lake City	Utah	United States	84106
541	Huntsman Cancer Institute/University of Utah	Salt Lake City	Utah	United States	84112
542	LDS Hospital	Salt Lake City	Utah	United States	84143
543	University of Vermont	Burlington	Vermont	United States	05401
544	Martha Jefferson Hospital	Charlottesville	Virginia	United States	22901
545	University of Virginia	Charlottesville	Virginia	United States	22908
546	Fredericksburg Oncology Inc	Fredericksburg	Virginia	United States	22401
547	Virginia Oncology Associates-Hampton	Hampton	Virginia	United States	23666
548	Rockingham Memorial Hospital Hahn Cancer Center	Harrisonburg	Virginia	United States	22801
549	Lynchburg Hematology-Oncology Clinic	Lynchburg	Virginia	United States	24501
550	Southwest VA Regional Cancer Center	Norton	Virginia	United States	24273
551	Auburn Regional Medical Center	Auburn	Washington	United States	98001
552	PeaceHealth Saint Joseph Medical Center	Bellingham	Washington	United States	98225
553	Harrison HealthPartners Hematology and Oncology-Bremerton	Bremerton	Washington	United States	98310
554	Providence Centralia Hospital	Centralia	Washington	United States	98531
555	Saint Francis Hospital	Federal Way	Washington	United States	98003
556	Columbia Basin Hematology and Oncology PLLC	Kennewick	Washington	United States	99336
557	Providence - Saint Peter Hospital	Olympia	Washington	United States	98506-5166
558	Good Samaritan Community Hospital	Puyallup	Washington	United States	98372
559	Minor and James Medical PLLC	Seattle	Washington	United States	98104
560	Group Health Cooperative-Seattle	Seattle	Washington	United States	98112
561	Swedish Medical Center-First Hill	Seattle	Washington	United States	98122-4307
562	The Polyclinic	Seattle	Washington	United States	98122
563	University of Washington Medical Center	Seattle	Washington	United States	98195
564	Cancer Care Northwest - Spokane South	Spokane	Washington	United States	99202
565	Rockwood Clinic	Spokane	Washington	United States	99220
566	Allenmore Hospital	Tacoma	Washington	United States	98405
567	Northwest CCOP	Tacoma	Washington	United States	98405
568	Saint Joseph Medical Center	Tacoma	Washington	United States	98405
569	Multicare Health System	Tacoma	Washington	United States	98415
570	Madigan Army Medical Center	Tacoma	Washington	United States	98431
571	Saint Clare Hospital	Tacoma	Washington	United States	98499
572	PeaceHealth Southwest Medical Center	Vancouver	Washington	United States	98664
573	Compass Oncology Vancouver	Vancouver	Washington	United States	98684
574	Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26101
575	Marshfield Clinic Cancer Center at Sacred Heart	Eau Claire	Wisconsin	United States	54701
576	Sacred Heart Hospital	Eau Claire	Wisconsin	United States	54701
577	Aurora Cancer Care-Southern Lakes	Elkhorn	Wisconsin	United States	53121
578	Agnesian Cancer Center	Fond Du Lac	Wisconsin	United States	54935
579	Aurora Cancer Care-Glendale	Glendale	Wisconsin	United States	53212
580	Green Bay Oncology at Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301-3526
581	Saint Vincent Hospital	Green Bay	Wisconsin	United States	54301
582	Green Bay Oncology Limited at Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
583	Saint Mary's Hospital	Green Bay	Wisconsin	United States	54303
584	Mercy Health System	Janesville	Wisconsin	United States	53547
585	Mayo Clinic Health System-Franciscan Healthcare	La Crosse	Wisconsin	United States	54601
586	Bay Area Medical Center	Marinette	Wisconsin	United States	54143
587	Marshfield Clinic	Marshfield	Wisconsin	United States	54449
588	Saint Joseph's Hospital	Marshfield	Wisconsin	United States	54449
589	Medical Consultants Limited	Milwaukee	Wisconsin	United States	53215
590	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin	United States	54548
591	Green Bay Oncology - Oconto Falls	Oconto Falls	Wisconsin	United States	54154
592	Marshfield Clinic at James Beck Cancer Center	Rhinelander	Wisconsin	United States	54501
593	Marshfield Clinic-Rice Lake Center	Rice Lake	Wisconsin	United States	54868
594	Vince Lombardi Cancer Clinic-Sheboygan	Sheboygan	Wisconsin	United States	53081
595	Saint Michael's Hospital	Stevens Point	Wisconsin	United States	54481
596	Green Bay Oncology - Sturgeon Bay	Sturgeon Bay	Wisconsin	United States	54235
597	Marshfield Clinic-Wausau Center	Wausau	Wisconsin	United States	54401
598	Marshfield Clinic - Weston Center	Weston	Wisconsin	United States	54476
599	Marshfield Clinic - Wisconsin Rapids Center	Wisconsin Rapids	Wisconsin	United States	54494
600	Welch Cancer Center	Sheridan	Wyoming	United States	82801
601	Cross Cancer Institute	Edmonton	Alberta	Canada	T6G 1Z2
602	Atlantic Health Sciences Corporation-Saint John Regional Hospital	Saint John	New Brunswick	Canada	E2L 4L2
603	Grand River Regional Cancer Centre at Grand River Hospital	Kitchener	Ontario	Canada	N2G 1G3
604	London Regional Cancer Program	London	Ontario	Canada	N6A 4L6
605	Credit Valley Hospital	Mississauga	Ontario	Canada	L5M 2N1
606	Lakeridge Health Oshawa	Oshawa	Ontario	Canada	L1G 2B9
607	Ottawa Health Research Institute-General Division	Ottawa	Ontario	Canada	K1H 1C4
608	Thunder Bay Regional Health Science Centre	Thunder Bay	Ontario	Canada	P7B 6V4
609	Saint Michael's Hospital	Toronto	Ontario	Canada	M5B 1W8
610	University Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9
611	CSSS Champlain-Charles Le Moyne	Greenfield Park	Quebec	Canada	J4V 2H1
612	CHUQ - Pavilion Hotel-Dieu de Quebec	Quebec City	Quebec	Canada	G1R 2J6
613	Allan Blair Cancer Centre	Regina	Saskatchewan	Canada	S4T 7T1
614	Saskatoon Cancer Centre	Saskatoon	Saskatchewan	Canada	S7N 4H4
615	Instituto Nacional de Enfermedades Neoplasicas	Lima		Peru	Lima 34
616	I Gonzales Martinez-Oncologic Hospital	San Juan		Puerto Rico	00919
617	San Juan City Hospital	San Juan		Puerto Rico	00936

Sponsors and Collaborators

• ECOG-ACRIN Cancer Research Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Al Benson, Eastern Cooperative Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: ECOG-ACRIN Cancer Research Group
• ClinicalTrials.gov Identifier: NCT00303628
• Other Study ID Numbers: E5204; NCI-2009-00563; CDR0000467561; E5204; U10CA021115
• First Posted: Mar 17, 2006
• Last Update Posted: Nov 17, 2020
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by ECOG-ACRIN Cancer Research Group: Rectal cancer; Bevacizumab
• Additional relevant MeSH terms: Rectal Neoplasms; Leucovorin; Bevacizumab; Antineoplastic Agents, Immunological; Fluorouracil; Oxaliplatin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Levoleucovorin

Study Results

Participant Flow

Recruitment Details	The study was activated on February 17, 2006. Due to slow accrual, it was terminated on April 29, 2009 before reaching its accrual goal with final accrual of 355 patients.

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Period Title: Overall Study
STARTED	176	179
Eligible	171	177
Treated	173	174
COMPLETED	126	106
NOT COMPLETED	50	73

Baseline Characteristics

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)	Total
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV	Total of all reporting groups
Overall Participants	176	179	355
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	54	53	53
Sex: Female, Male (Count of Participants)
Female	62 35.2%	67 37.4%	129 36.3%
Male	114 64.8%	112 62.6%	226 63.7%

Outcome Measures

1. Primary Outcome

Title	5-year Overall Survival Rate
Description	Overall survival (OS) was defined as time from randomization to date of death from any cause. Patients who were still alive were censored at last date of known alive. Kaplan-Meier method was used to estimate the 5-year OS rate.
Time Frame	Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization

Outcome Measure Data

Analysis Population Description

All randomized patients (intent-to-treat population)

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Measure Participants	176	179
Number (95% Confidence Interval) [proportion of participants]	0.883 0.5%	0.837 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Oxaliplatin, Fluorouracil, Leucovorin), Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.876
	Comments	Stratified log rank test. The above P value was for one-sided test
	Method	Log Rank
	Comments

2. Secondary Outcome

Title	5-year Disease-free Survival Rate
Description	Disease-free survival (DFS) was defined as time from randomization to recurrence, second invasive primary cancer or death, whichever occurred first. Patients who were still alive and had no DFS events were censored at the last disease assessment date known to be free of DFS events. Kaplan-Meier method was used to estimate 5-year DFS rate.
Time Frame	Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization

Outcome Measure Data

Analysis Population Description

All randomized patients (intent-to-treat population)

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Measure Participants	176	179
Number (95% Confidence Interval) [proportion of participants]	0.712 0.4%	0.765 0.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Oxaliplatin, Fluorouracil, Leucovorin), Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.299
	Comments	two-sided stratified log rank test p value
	Method	Log Rank
	Comments

3. Secondary Outcome

Title	Patterns of Failure
Description	Failure included recurrence, second primary cancer and death without recurrence.
Time Frame	Follow-up assessments performed every 3 months for patients < 2 years from randomization, every 6 months for patients 2-5 years from randomization, and every 12 months for patients 5-10 years from randomization

Outcome Measure Data

Analysis Population Description

all randomized patients

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Measure Participants	176	179
Local/regional recurrence	6 3.4%	5 2.8%
Distant recurrence	24 13.6%	20 11.2%
Mutiple recurrence	5 2.8%	8 4.5%
Unknown site	1 0.6%	1 0.6%
Death without recurrence	5 2.8%	6 3.4%
Second invasive primary cancer	12 6.8%	4 2.2%
DFS event	52 29.5%	41 22.9%

4. Secondary Outcome

Title	Proportion of Patients Who Completed 12 Cycles of Treatment
Description	In the study, treatment was repeated every 2 weeks for a total of 12 cycles on both arms. The total number of cycles of treatment patient received until going off treatment due to any reason was recorded. It was a measure of the tolerance of the therapy.
Time Frame	assessed at the end of treatment

Outcome Measure Data

Analysis Population Description

Patients who received at least one cycle of protocol treatment

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Measure Participants	173	174
Number [proportion of participants]	0.722 0.4%	0.615 0.3%

5. Other Pre-specified Outcome

Title	Change in Rectal Function Between Baseline and 12 Months
Description	Change in rectal function between baseline and 12 months was measuring the long-term rectal function among the patients. Rectal function was measured using the Bowel Function Questionnaire at baseline and 12 months after randomization. The total score of the questionnaire was calculated as the number of problems with bowel function (score range 0-11). Change in rectal function between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated improved rectal function. This change in score was calculated for each individual patient who had the data.
Time Frame	assessed at baseline and 12 months after randomization

Outcome Measure Data

Analysis Population Description

Patients with data about their rectal function measured using the Bowel Function Questionnaire at both baseline and 12 months after randomization. Due to the early termination of the trial, the sample size was quite small for the endpoint. Consequently, it was considered as an exploratory endpoint.

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Measure Participants	12	11
Mean (Standard Deviation) [scores on a scale]	-1.17 (3.19)	1.18 (3.09)

6. Other Pre-specified Outcome

Title	Change in Oxaliplatin-related Neurotoxicity Between Baseline and 12 Months
Description	Change in oxaliplatin-related neurotoxicity between baseline and 12 months was measuring the long-term symptom of oxaliplatin-related neurotoxicity among the patients. Oxaliplatin-related neurotoxicity was measured using the FACT/GOG-Ntx subscale at baseline and 12 months after randomization. The range of the total score of the scale was between 0 and 44, and lower values indicate higher neurotoxicity. Change in oxaliplatin-related neurotoxicity between baseline and 12 months= total score at 12 months - total score at baseline. A negative value indicated worsened symptom. This change in score was calculated for each individual patient who had the data.
Time Frame	assessed at baseline and 12 months after randomization

Outcome Measure Data

Analysis Population Description

Patients with data about their oxaliplatin-related neurotoxicity measured using FACT/GOG Ntx subscale at both baseline and 12 months after randomization. Due to the early termination of the trial, the sample size was quite small for the endpoint. Consequently, it was considered as an exploratory endpoint.

Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)	Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin IV over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV	Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I. oxaliplatin: Given IV fluorouracil: Given IV leucovorin calcium: Given IV bevacizumab: Given IV
Measure Participants	53	62
Mean (Standard Deviation) [scores on a scale]	-8.6 (8.1)	-9.5 (7.9)

Adverse Events

Time Frame	Assessed every cycle (1 cycle=2 weeks) while on treatment and for 30 days after the end of treatment
Adverse Event Reporting Description	Long-term follow up form was used to collect any severe (grade>=3) long term toxicity experienced after discontinuing protocol therapy and prior to diagnosis of progression/relapse if the toxicity has not been previously reported yet. It was assessed every 3 months <2 year, every 6 months 2-5 years, and annually 5-10 years after study activation.
Arm/Group Title	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)		Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
Arm/Group Description	Patients receive oxaliplatin intravenously (IV) over 2 hours, leucovorin calcium IV over 2 hours, and fluorouracil IV on day 1 followed by fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses* in the absence of disease progression or unacceptable toxicity.		Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive oxaliplatin, leucovorin calcium, and fluorouracil as in arm I
All Cause Mortality
	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)		Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)		Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	119/173 (68.8%)		123/174 (70.7%)
Blood and lymphatic system disorders
Anemia	2/173 (1.2%)		2/174 (1.1%)
Febrile neutropenia	2/173 (1.2%)		4/174 (2.3%)
Cardiac disorders
Cardiac-ischemia	1/173 (0.6%)		2/174 (1.1%)
Cardiomyopathy, restrictive	0/173 (0%)		1/174 (0.6%)
Cardiac/heart, pain	0/173 (0%)		1/174 (0.6%)
Eye disorders
Tearing	0/173 (0%)		1/174 (0.6%)
Ocular-other	0/173 (0%)		1/174 (0.6%)
Gastrointestinal disorders
Diarrhea w/o prior colostomy	16/173 (9.2%)		20/174 (11.5%)
Dysphagia	0/173 (0%)		2/174 (1.1%)
Enteritis	1/173 (0.6%)		0/174 (0%)
Fistula, Colon/cecum/appendix	0/173 (0%)		1/174 (0.6%)
Fistula, Rectum	0/173 (0%)		2/174 (1.1%)
Dyspepsia	0/173 (0%)		1/174 (0.6%)
Ileus	1/173 (0.6%)		1/174 (0.6%)
Muco/stomatitis (symptom) oral cavity	2/173 (1.2%)		2/174 (1.1%)
Nausea	6/173 (3.5%)		6/174 (3.4%)
Obstruction, small bowel NOS	1/173 (0.6%)		1/174 (0.6%)
Proctitis	1/173 (0.6%)		0/174 (0%)
Vomiting	7/173 (4%)		1/174 (0.6%)
GI-other	0/173 (0%)		2/174 (1.1%)
Lower GI, hemorrhage NOS	1/173 (0.6%)		3/174 (1.7%)
Rectum, hemorrhage	2/173 (1.2%)		0/174 (0%)
Abdomen, pain	1/173 (0.6%)		4/174 (2.3%)
Rectum, pain	1/173 (0.6%)		0/174 (0%)
General disorders
Fatigue	12/173 (6.9%)		19/174 (10.9%)
Fever w/o neutropenia	2/173 (1.2%)		0/174 (0%)
Chest/thoracic pain NOS	1/173 (0.6%)		2/174 (1.1%)
Hepatobiliary disorders
Gallbladder, pain	1/173 (0.6%)		0/174 (0%)
Immune system disorders
Allergic reaction	2/173 (1.2%)		4/174 (2.3%)
Infections and infestations
Infection w/ gr3-4 neut, colon	1/173 (0.6%)		1/174 (0.6%)
Infection w/ gr3-4 neut, sinus	0/173 (0%)		1/174 (0.6%)
Infection w/ gr3-4 neut, skin	0/173 (0%)		1/174 (0.6%)
Infection Gr0-2 neut, colon	0/173 (0%)		1/174 (0.6%)
Infection Gr0-2 neut, joint	1/173 (0.6%)		0/174 (0%)
Infection Gr0-2 neut, pelvis NOS	0/173 (0%)		1/174 (0.6%)
Infection Gr0-2 neut, soft tissue	0/173 (0%)		1/174 (0.6%)
Infection Gr0-2 neut, urinary tract	0/173 (0%)		3/174 (1.7%)
Infection w/ unk ANC bladder	1/173 (0.6%)		0/174 (0%)
Infection w/ unk ANC catheter related	0/173 (0%)		1/174 (0.6%)
Infection-other	0/173 (0%)		2/174 (1.1%)
Injury, poisoning and procedural complications
Wound - non-infectious	0/173 (0%)		1/174 (0.6%)
Leak, incl. anastomotic, Leak NOS	0/173 (0%)		1/174 (0.6%)
Leak, incl. anastomotic, rectum	0/173 (0%)		1/174 (0.6%)
Fracture	1/173 (0.6%)		0/174 (0%)
Prolong intubation post pulm resection	0/173 (0%)		1/174 (0.6%)
Vascular access,Thrombosis/embolism	1/173 (0.6%)		2/174 (1.1%)
Investigations
Leukocytes decreased	49/173 (28.3%)		37/174 (21.3%)
Lymphopenia	16/173 (9.2%)		9/174 (5.2%)
Neutrophils decreased	63/173 (36.4%)		51/174 (29.3%)
Platelets decreased	12/173 (6.9%)		1/174 (0.6%)
Weight gain	1/173 (0.6%)		0/174 (0%)
Weight loss	1/173 (0.6%)		0/174 (0%)
INR increased	0/173 (0%)		1/174 (0.6%)
Alanine aminotransferase increased	0/173 (0%)		1/174 (0.6%)
Aspartate aminotransferase increased	0/173 (0%)		2/174 (1.1%)
Creatinine increased	0/173 (0%)		2/174 (1.1%)
Metabolism and nutrition disorders
Anorexia	4/173 (2.3%)		5/174 (2.9%)
Dehydration	7/173 (4%)		8/174 (4.6%)
Hypocalcemia	1/173 (0.6%)		1/174 (0.6%)
Hyperglycemia	3/173 (1.7%)		3/174 (1.7%)
Hypophosphatemia	1/173 (0.6%)		0/174 (0%)
Hypokalemia	4/173 (2.3%)		3/174 (1.7%)
Hyponatremia	1/173 (0.6%)		4/174 (2.3%)
Musculoskeletal and connective tissue disorders
Osteonecrosis (avascular necrosis)	0/173 (0%)		1/174 (0.6%)
Back, pain	1/173 (0.6%)		1/174 (0.6%)
Bone, pain	0/173 (0%)		1/174 (0.6%)
Extremity-limb, pain	1/173 (0.6%)		0/174 (0%)
Joint, pain	0/173 (0%)		4/174 (2.3%)
Neck, pain	1/173 (0.6%)		0/174 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Secondary malignancy	1/173 (0.6%)		0/174 (0%)
Nervous system disorders
Ataxia	0/173 (0%)		1/174 (0.6%)
Dizziness	0/173 (0%)		1/174 (0.6%)
Laryngeal nerve dysfunction	1/173 (0.6%)		0/174 (0%)
Leukoencephalopathy	0/173 (0%)		1/174 (0.6%)
Neuropathy-motor	1/173 (0.6%)		1/174 (0.6%)
Neuropathy-sensory	26/173 (15%)		31/174 (17.8%)
Syncope	2/173 (1.2%)		1/174 (0.6%)
Neurologic-other	0/173 (0%)		1/174 (0.6%)
Head/headache	1/173 (0.6%)		1/174 (0.6%)
Psychiatric disorders
Depression	0/173 (0%)		1/174 (0.6%)
Renal and urinary disorders
Proteinuria	0/173 (0%)		1/174 (0.6%)
Incontinence urinary	0/173 (0%)		1/174 (0.6%)
Obstruction-ureteral	0/173 (0%)		1/174 (0.6%)
Renal failure	0/173 (0%)		2/174 (1.1%)
Urinary frequency/urgency	0/173 (0%)		1/174 (0.6%)
Urinary retention	0/173 (0%)		1/174 (0.6%)
Respiratory, thoracic and mediastinal disorders
Muco/stomatitis (symptom) pharynx	0/173 (0%)		1/174 (0.6%)
Dyspnea	1/173 (0.6%)		8/174 (4.6%)
Hypoxia	0/173 (0%)		1/174 (0.6%)
Voice changes/dysarthria	0/173 (0%)		1/174 (0.6%)
Pulmonary/Upper Respiratory-other	0/173 (0%)		1/174 (0.6%)
Skin and subcutaneous tissue disorders
Hand-foot reaction	0/173 (0%)		5/174 (2.9%)
Vascular disorders
Hypertension	0/173 (0%)		11/174 (6.3%)
Thrombosis/thrombus/embolism	4/173 (2.3%)		9/174 (5.2%)
Other (Not Including Serious) Adverse Events
	Arm I (Oxaliplatin, Fluorouracil, Leucovorin)		Arm II (Oxaliplatin, Fluorouracil, Leucovorin, Bevacizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	154/173 (89%)		155/174 (89.1%)
Blood and lymphatic system disorders
Anemia	106/173 (61.3%)		103/174 (59.2%)
Eye disorders
Tearing	5/173 (2.9%)		11/174 (6.3%)
Gastrointestinal disorders
Constipation	34/173 (19.7%)		36/174 (20.7%)
Diarrhea w/o prior colostomy	84/173 (48.6%)		84/174 (48.3%)
Dysphagia	11/173 (6.4%)		13/174 (7.5%)
Dyspepsia	19/173 (11%)		12/174 (6.9%)
Muco/stomatitis by exam, oral cavity	34/173 (19.7%)		34/174 (19.5%)
Muco/stomatitis (symptom) oral cavity	35/173 (20.2%)		34/174 (19.5%)
Nausea	98/173 (56.6%)		100/174 (57.5%)
Vomiting	37/173 (21.4%)		37/174 (21.3%)
Abdomen, pain	19/173 (11%)		20/174 (11.5%)
General disorders
Fatigue	122/173 (70.5%)		121/174 (69.5%)
Rigors/chills	8/173 (4.6%)		9/174 (5.2%)
Immune system disorders
Allergic reaction	9/173 (5.2%)		5/174 (2.9%)
Investigations
Leukocytes decreased	104/173 (60.1%)		98/174 (56.3%)
Lymphopenia	19/173 (11%)		22/174 (12.6%)
Neutrophils decreased	83/173 (48%)		72/174 (41.4%)
Platelets decreased	92/173 (53.2%)		48/174 (27.6%)
Weight loss	14/173 (8.1%)		20/174 (11.5%)
Alkaline phosphatase increased	31/173 (17.9%)		15/174 (8.6%)
Alanine aminotransferase increased	21/173 (12.1%)		13/174 (7.5%)
Aspartate aminotransferase increased	37/173 (21.4%)		20/174 (11.5%)
Metabolism and nutrition disorders
Anorexia	47/173 (27.2%)		45/174 (25.9%)
Dehydration	10/173 (5.8%)		17/174 (9.8%)
Hypoalbuminemia	14/173 (8.1%)		7/174 (4%)
Hyperglycemia	18/173 (10.4%)		22/174 (12.6%)
Hypokalemia	16/173 (9.2%)		15/174 (8.6%)
Hyponatremia	10/173 (5.8%)		9/174 (5.2%)
Musculoskeletal and connective tissue disorders
Joint, pain	15/173 (8.7%)		26/174 (14.9%)
Muscle, pain	9/173 (5.2%)		5/174 (2.9%)
Nervous system disorders
Taste disturbance	23/173 (13.3%)		23/174 (13.2%)
Neuropathy-sensory	132/173 (76.3%)		130/174 (74.7%)
Head/headache	16/173 (9.2%)		24/174 (13.8%)
Psychiatric disorders
Insomnia	22/173 (12.7%)		35/174 (20.1%)
Renal and urinary disorders
Proteinuria	2/173 (1.2%)		15/174 (8.6%)
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/173 (2.9%)		12/174 (6.9%)
Nose, hemorrhage	13/173 (7.5%)		35/174 (20.1%)
Cough	10/173 (5.8%)		11/174 (6.3%)
Dyspnea	16/173 (9.2%)		26/174 (14.9%)
Voice changes/dysarthria	7/173 (4%)		15/174 (8.6%)
Skin and subcutaneous tissue disorders
Dry skin	13/173 (7.5%)		9/174 (5.2%)
Alopecia	33/173 (19.1%)		35/174 (20.1%)
Hyperpigmentation	2/173 (1.2%)		9/174 (5.2%)
Nail changes	12/173 (6.9%)		15/174 (8.6%)
Rash/desquamation	19/173 (11%)		15/174 (8.6%)
Hand-foot reaction	20/173 (11.6%)		26/174 (14.9%)
Vascular disorders
Hypertension	8/173 (4.6%)		29/174 (16.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.