Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colon Cancer That Cannot Be Removed By Surgery

• Sponsor: NSABP Foundation Inc (Other)
• Overall Status: Completed
• CT.gov ID: NCT00321828
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 90
• Locations: 163
• Arm: 1
• Duration (Months): 81.1
• Patients Per Site: 0.6
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and oxaliplatin, 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 colon cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colon cancer that cannot be removed by surgery.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Biological: bevacizumab; Drug: fluorouracil; Drug: leucovorin; Drug: oxaliplatin	Phase 2

Detailed Description

OBJECTIVES:

Primary

• Determine the rate of major morbidity in patients with unresectable stage IV colon cancer and a synchronous asymptomatic primary tumor treated with fluorouracil, leucovorin calcium, and oxaliplatin (mFOLFOX6) in combination with bevacizumab without resection of the primary tumor.

Secondary

• Determine the rate of specific events related to the intact primary tumor requiring hospitalization or a major intervention but not requiring surgery.

• Determine the rate of ≥ grade 3 toxicity as defined by the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0) that is related to study therapy prior to disease progression.

• Determine overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

Patients receive bevacizumab IV over 30-90 minutes, oxaliplatin IV given concurrently with leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically for 5 years after study entry.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 90 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin (mFOLFOX6) Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and a Synchronous Asymptomatic Primary Tumor
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Nov 1, 2009
• Actual Study Completion Date: Dec 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab

Biological: bevacizumab; bevacizumab 5 mg/kg IV on day 1 every 14 days until excessive toxicity or disease progression; Drug: fluorouracil; 5-FU 400 mg/m2 IV bolus over 2-4 minutes then 2400 mg/m2 IV continuous infusion over 46 hours on day 1 every 14 days until excessive toxicity or disease progression; Other Names: 5-FU ; Drug: leucovorin; leucovorin 400 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression; Other Names: leucovorin calcium ; Drug: oxaliplatin; Oxaliplatin 85 mg/m2 IV on day 1 every 14 days until excessive toxicity or disease progression

Outcome Measures

Primary Outcome Measures

1. Major Morbidity Related to the Intact Primary Tumor [24 months]

   Cumulative incidence was used to compute percent probability of morbidity. Cumulative incidence at time t measures the probability of a participant having an event (i.e., Colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death) over the given duration, t. It involves computing the probability of an event at any observed time (i.e., the number of new cases during a period divided by the number of subjects at risk) and multiplying these successive probabilities by any early computed probability to get the final estimate.

Secondary Outcome Measures

1. Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration [Time from start of study through year 5]

2. Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery [Time from start of study through year 5]

3. Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery [Time from start of study through year 5]

4. Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery [Time from start of study through year 5]

5. Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0 [Time from start of study through year 5]

6. Overall Survival as Measured by Death From Any Cause [Time from start of study through year 5]

Eligibility Criteria

Criteria

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

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed adenocarcinoma of the colon

• No histological findings other than adenocarcinoma of the colon

• If the primary colon tumor and the metastatic lesions have been identified at the same time and it is not possible to biopsy the colonic lesion, the patient will be eligible without histologic confirmation of the primary cancer of the colon as long as other radiographic studies or scans document the characteristics of a colon cancer AND the biopsy of a metastatic site confirms diagnosis of adenocarcinoma suggestive of a primary tumor of the colon

• Unresected primary tumor of the colon AND radiographically confirmed metastatic colon cancer (single or multiple sites of metastases) that are not considered surgically resectable for cure by chest imaging and CT scan or MRI of the abdomen within the past 4 weeks and by endoscopy within the past 8 weeks

• Asymptomatic primary tumor

• No obstruction, perforation, or active bleeding requiring transfusion

• Distal extent of the tumor must be ≥ 12 cm from the anal verge on endoscopy

• Not a candidate for curative surgical resection of all metastatic and colon primary tumors

• No evidence of Central Nervous System (CNS) metastases

• No recurrent local or metastatic disease after prior adjuvant therapy

• No diagnosis of rectal carcinoma

PATIENT CHARACTERISTICS:

• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

• Absolute neutrophil count ≥ 1200/mm³

• Platelet count ≥ 100,000/mm³

• Hemoglobin ≥ 9 g/dL

• Aspartate aminotransferase (AST) ≤ 2.5 times upper limit of normal (ULN) (≤ 5.0 times ULN if liver metastases are present)

• Alkaline phosphatase ≤ 3.0 times ULN (≤ 5.0 times ULN if liver metastases are present)

• Bilirubin ≤ 1.5 times ULN (≤ 2.0 times ULN if liver metastases are present)

• Creatinine < 1.8 mg/dL

• Urine dipstick indicating 0-1+ protein

• If dipstick reading is ≥ 2+, a 24-hour urine collection must demonstrate < 1 g of protein

• Prothrombin Time and International Normalized Ratio (PT/INR) ≤ 1.5 unless the patient is on therapeutic doses of warfarin, in which case the following criteria must be met:

• Patient must have an in-range INR (between 2 and 3) on a stable dose of warfarin

• Patient must not have active bleeding or a pathologic condition that is associated with a high risk of bleeding

• Patients with a history of non-colorectal malignancies must be disease free for ≥ 5 years prior to study entry and be deemed at low risk for recurrence

• Patients with the following cancers are eligible if diagnosed and treated within the past 5 years:

• Carcinoma in situ of the colon

• Melanoma in situ

• Basal cell or squamous cell carcinoma of the skin

• Carcinoma in situ of the cervix

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception during and for 3 months after the completion of study therapy

• No uncontrolled blood pressure (BP), defined as BP > 150/100 mm Hg

• No nonmalignant systemic disease that would preclude any of the study therapy drugs, compromise the safety of the patient, or inhibit the patient's ability to participate in the study, including any of the following:

• New York Heart Association class III or IV cardiac disease

• Myocardial infarction within the past 6 months

• Unstable angina within the past 6 months

• Symptomatic arrhythmia

• No transient ischemic attack or cerebrovascular accident within the past 6 months

• No symptomatic peripheral vascular ischemia within the past 6 months

• No arterial thrombotic event within the past 6 months

• No gastroduodenal ulcer(s) determined by endoscopy to be active

• No gastrointestinal perforation within the past 12 months

• No serious or nonhealing wound, skin ulcer, or bone fracture

• No significant traumatic injury within the past 28 days

• No significant episodes of acute bleeding requiring blood transfusion within the past 6 months

• No clinically significant (≥ grade 2) peripheral neuropathy (neurosensory or neuromotor toxicity)

• No pulmonary fibrosis or interstitial pneumonitis by chest x-ray

• No psychiatric or addictive disorders or other conditions that would preclude the patient from meeting study requirements

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• No prior systemic chemotherapy, radiation therapy, or surgery for this malignancy

• No prior endoscopic management of this malignancy other than biopsy, including endoscopic stent placement, fulguration, or laser treatment

• More than 30 days since prior investigational drugs

• More than 28 days since prior major surgical procedure or open biopsy

• More than 7 days since prior core biopsy or other minor procedure, excluding placement of a vascular access device

• No concurrent major surgery unrelated to intact primary colon cancer

• No concurrent radiotherapy

• No concurrent filgrastim (G-CSF) or pegfilgrastim as primary prophylaxis for neutropenia

• No concurrent halogenated antiviral agents

• No other concurrent investigational drugs

• No other concurrent antineoplastic agents

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Cancer Research Center at University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
2	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
3	Kaiser Permanente - Fremont	Fremont	California	United States	94538
4	Kaiser Permanente Medical Center - Hayward	Hayward	California	United States	94545
5	Scripps Cancer Center - San Diego	La Jolla	California	United States	92037
6	Kaiser Permanente Medical Center - Oakland	Oakland	California	United States	94611
7	Kaiser Permanente Medical Center - Redwood City	Redwood City	California	United States	94063
8	Kaiser Permanente Medical Center - Richmond	Richmond	California	United States	94801
9	Kaiser Permanente Medical Center - Roseville	Roseville	California	United States	95661
10	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California	United States	95823
11	Kaiser Permanente Medical Center - Sacramento	Sacramento	California	United States	95825
12	Kaiser Permanente Medical Office -Vandever Medical Office	San Diego	California	United States	92120
13	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California	United States	94115
14	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California	United States	95119
15	Kaiser Foundation Hospital - San Rafael	San Rafael	California	United States	94903
16	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California	United States	95051
17	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California	United States	95403
18	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California	United States	94080
19	Kaiser Permanente Medical Facility - Stockton	Stockton	California	United States	95210
20	Kaiser Permanente Medical Center - Vallejo	Vallejo	California	United States	94589
21	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California	United States	94596
22	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
23	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
24	Sibley Memorial Hospital	Washington	District of Columbia	United States	20016
25	Lakeland Regional Cancer Center at Lakeland Regional Medical Center	Lakeland	Florida	United States	33805
26	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia	United States	31403-3089
27	John H. Stroger, Jr. Hospital of Cook County	Chicago	Illinois	United States	60612-3785
28	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois	United States	62526
29	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois	United States	60068-1174
30	Regional Cancer Center at Memorial Medical Center	Springfield	Illinois	United States	62781-0001
31	St. Francis Hospital and Health Centers - Beech Grove Campus	Beech Grove	Indiana	United States	46107
32	Elkhart General Hospital	Elkhart	Indiana	United States	46515
33	Howard Community Hospital	Kokomo	Indiana	United States	46904
34	Center for Cancer Therapy at LaPorte Hospital and Health Services	La Porte	Indiana	United States	46350
35	Reid Hospital & Health Care Services	Richmond	Indiana	United States	47374
36	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
37	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
38	Saint Joseph Regional Medical Center	South Bend	Indiana	United States	46617
39	McFarland Clinic, PC	Ames	Iowa	United States	50010
40	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1002
41	McCreery Cancer Center at Ottumwa Regional	Ottumwa	Iowa	United States	52501
42	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas	United States	66720
43	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas	United States	67801
44	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas	United States	67042
45	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas	United States	67068
46	Lawrence Memorial Hospital	Lawrence	Kansas	United States	66044
47	Southwest Medical Center	Liberal	Kansas	United States	67901
48	Cancer Center of Kansas, PA - Newton	Newton	Kansas	United States	67114
49	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas	United States	67357
50	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas	United States	67124
51	Cancer Center of Kansas, PA - Salina	Salina	Kansas	United States	67042
52	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas	United States	67152
53	Associates in Womens Health, PA - North Review	Wichita	Kansas	United States	67208
54	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas	United States	67208
55	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas	United States	67214
56	CCOP - Wichita	Wichita	Kansas	United States	67214
57	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas	United States	67214
58	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas	United States	67156
59	Louisville Oncology at Norton Cancer Institute - Louisville	Louisville	Kentucky	United States	40202
60	Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center	Baltimore	Maryland	United States	21237
61	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
62	Cancer Institute at St. Joseph Medical Center	Towson	Maryland	United States	21204
63	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts	United States	02721
64	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan	United States	48202
65	Borgess Medical Center	Kalamazoo	Michigan	United States	49001
66	West Michigan Cancer Center	Kalamazoo	Michigan	United States	49007-3731
67	Bronson Methodist Hospital	Kalamazoo	Michigan	United States	49007
68	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
69	Fairview Ridges Hospital	Burnsville	Minnesota	United States	55337
70	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota	United States	55433
71	Fairview Southdale Hospital	Edina	Minnesota	United States	55435
72	Mercy and Unity Cancer Center at Unity Hospital	Fridley	Minnesota	United States	55432
73	Hutchinson Area Health Care	Hutchinson	Minnesota	United States	55350
74	Meeker County Memorial Hospital	Lichfield	Minnesota	United States	55355
75	HealthEast Cancer Care at St. John's Hospital	Maplewood	Minnesota	United States	55109
76	Minnesota Oncology Hematology, PA - Maplewood	Maplewood	Minnesota	United States	55109
77	Virginia Piper Cancer Institute at Abbott - Northwestern Hospital	Minneapolis	Minnesota	United States	55407
78	Hennepin County Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55415
79	Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center	Robbinsdale	Minnesota	United States	55422-2900
80	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
81	Park Nicollet Cancer Center	Saint Louis Park	Minnesota	United States	55416
82	United Hospital	Saint Paul	Minnesota	United States	55102
83	St. Francis Cancer Center at St. Francis Medical Center	Shakopee	Minnesota	United States	55379
84	Regions Hospital Cancer Care Center	St. Paul	Minnesota	United States	55101
85	Ridgeview Medical Center	Waconia	Minnesota	United States	55387
86	Minnesota Oncology Hematology, PA - Woodbury	Woodbury	Minnesota	United States	55125
87	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
88	Arch Medical Services, Incorporated at Center for Cancer Care and Research	Saint Louis	Missouri	United States	63141
89	CCOP - Cancer Research for the Ozarks	Springfield	Missouri	United States	65802
90	St. John's Regional Health Center	Springfield	Missouri	United States	65804
91	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri	United States	65807
92	CCOP - Montana Cancer Consortium	Billings	Montana	United States	59101
93	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana	United States	59101
94	Northern Rockies Radiation Oncology Center	Billings	Montana	United States	59101
95	St. Vincent Healthcare Cancer Care Services	Billings	Montana	United States	59101
96	St. James Healthcare Cancer Care	Butte	Montana	United States	59701
97	Great Falls Clinic - Main Facility	Great Falls	Montana	United States	59405
98		Great Falls	Montana	United States	59405
99	Glacier Oncology, PLLC	Kalispell	Montana	United States	59901
100	Kalispell Medical Oncology at KRMC	Kalispell	Montana	United States	59901
101	Kalispell Regional Medical Center	Kalispell	Montana	United States	59901
102	Community Medical Center	Missoula	Montana	United States	59801
103	Guardian Oncology and Center for Wellness	Missoula	Montana	United States	59804
104	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana	United States	59807-7877
105	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana	United States	59807
106	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
107	St. Barnabas Medical Center Cancer Center	Livingston	New Jersey	United States	07039
108	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
109	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York	United States	13057
110	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York	United States	12801
111	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
112	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
113	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio	United States	44307
114	Mary Rutan Hospital	Bellefontaine	Ohio	United States	43311
115	Aultman Cancer Center at Aultman Hospital	Canton	Ohio	United States	44710-1799
116	Adena Regional Medical Center	Chillicothe	Ohio	United States	45601
117	Oncology Hematology Care, Incorporated - Blue Ash	Cincinnati	Ohio	United States	45242
118	Riverside Methodist Hospital Cancer Care	Columbus	Ohio	United States	43214-3998
119	CCOP - Columbus	Columbus	Ohio	United States	43215
120	Grant Medical Center Cancer Care	Columbus	Ohio	United States	43215
121	Mount Carmel Health - West Hospital	Columbus	Ohio	United States	43222
122	Doctors Hospital at Ohio Health	Columbus	Ohio	United States	43228
123	Grandview Hospital	Dayton	Ohio	United States	45405
124	Good Samaritan Hospital	Dayton	Ohio	United States	45406
125	David L. Rike Cancer Center at Miami Valley Hospital	Dayton	Ohio	United States	45409
126	Samaritan North Cancer Care Center	Dayton	Ohio	United States	45415
127	Veterans Affairs Medical Center - Dayton	Dayton	Ohio	United States	45428
128	CCOP - Dayton	Dayton	Ohio	United States	45429
129	Grady Memorial Hospital	Delaware	Ohio	United States	43015
130	Blanchard Valley Medical Associates	Findlay	Ohio	United States	45840
131	Middletown Regional Hospital	Franklin	Ohio	United States	45005-1066
132	Wayne Hospital	Greenville	Ohio	United States	45331
133	Charles F. Kettering Memorial Hospital	Kettering	Ohio	United States	45429
134	Fairfield Medical Center	Lancaster	Ohio	United States	43130
135	Strecker Cancer Center at Marietta Memorial Hospital	Marietta	Ohio	United States	45750
136	Licking Memorial Cancer Care Program at Licking Memorial Hospital	Newark	Ohio	United States	43055
137	Mercy Medical Center	Springfield	Ohio	United States	45504
138	Community Hospital of Springfield and Clark County	Springfield	Ohio	United States	45505
139	UVMC Cancer Care Center at Upper Valley Medical Center	Troy	Ohio	United States	45373-1300
140	Mount Carmel St. Ann's Cancer Center	Westerville	Ohio	United States	43081
141	Clinton Memorial Hospital	Wilmington	Ohio	United States	45177
142	Ruth G. McMillan Cancer Center at Greene Memorial Hospital	Xenia	Ohio	United States	45385
143	Genesis - Good Samaritan Hospital	Zanesville	Ohio	United States	43701
144	Bryn Mawr Hospital	Bryn Mawr	Pennsylvania	United States	19010
145	Riddle Memorial Hospital Cancer Center	Media	Pennsylvania	United States	19063
146	Cancer Center of Paoli Memorial Hospital	Paoli	Pennsylvania	United States	19301-1792
147	Kimmel Cancer Center at Thomas Jefferson University - Philadelphia	Philadelphia	Pennsylvania	United States	19107-5541
148	Allegheny Cancer Center at Allegheny General Hospital	Pittsburgh	Pennsylvania	United States	15212
149	Hematology and Oncology Associates of Northeastern Pennsylvania	Scranton	Pennsylvania	United States	18508
150	Mount Nittany Medical Center	State College	Pennsylvania	United States	16803
151	Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center	Upland	Pennsylvania	United States	19013
152	CCOP - Main Line Health	Wynnewood	Pennsylvania	United States	19096
153	Lankenau Cancer Center at Lankenau Hospital	Wynnewood	Pennsylvania	United States	19096
154	CCOP - Greenville	Greenville	South Carolina	United States	29615
155	Avera Cancer Institute	Sioux Falls	South Dakota	United States	57105
156	Medical X-Ray Center, PC	Sioux Falls	South Dakota	United States	57105
157	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota	United States	57117-5039
158	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas	United States	79410-1894
159	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
160	Danville Regional Medical Center	Danville	Virginia	United States	24541
161	West Virginia University Health Sciences Center - Charleston	Charleston	West Virginia	United States	25304
162	Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital	Parkersburg	West Virginia	United States	26102
163	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• NSABP Foundation Inc
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Norman Wolmark, MD, NSABP Foundation Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: NSABP Foundation Inc
• ClinicalTrials.gov Identifier: NCT00321828
• Other Study ID Numbers: NSABP C-10; U10CA012027; CDR0000463513
• First Posted: May 4, 2006
• Last Update Posted: Jan 24, 2013
• Last Verified: Jan 1, 2013

• Keywords provided by NSABP Foundation Inc: adenocarcinoma of the colon; stage IV colon cancer
• Additional relevant MeSH terms: Colonic Neoplasms; Leucovorin; Bevacizumab; Fluorouracil; Oxaliplatin; Levoleucovorin

Study Results

Participant Flow

Arm/Group Title	Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Arm/Group Description	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Period Title: Overall Study
STARTED	90
COMPLETED	86
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Arm/Group Description	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Overall Participants	90
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59 (11.2)
Sex: Female, Male (Count of Participants)
Female	45 50%
Male	45 50%

Outcome Measures

1. Primary Outcome

Title	Major Morbidity Related to the Intact Primary Tumor
Description	Cumulative incidence was used to compute percent probability of morbidity. Cumulative incidence at time t measures the probability of a participant having an event (i.e., Colonic bleeding, perforation, bowel obstruction, or fistula formation requiring surgery or resulting in patient death) over the given duration, t. It involves computing the probability of an event at any observed time (i.e., the number of new cases during a period divided by the number of subjects at risk) and multiplying these successive probabilities by any early computed probability to get the final estimate.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1: Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Arm/Group Description	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Measure Participants	86
Number (95% Confidence Interval) [probability of major morbidity (%)]	16.3

2. Secondary Outcome

Title	Local Complications as Assessed by Colonic Obstruction Requiring Hospitalization (But Not Surgery) for Medical Management, Stent Placement, Laser Treatment, or Fulguration
Time Frame	Time from start of study through year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Local Complications as Assessed by Gastrointestinal Bleeding Requiring Transfusion But Not Requiring Surgery
Time Frame	Time from start of study through year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Local Complications as Assessed by Fistula Formation (Self-draining Enterocutaneous Fistula and Intra-abdominal Abscess Requiring Percutaneous Drainage) Not Requiring Surgery
Time Frame	Time from start of study through year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Local Complications as Assessed by Other Events Related to the Intact Primary Tumor Which Require Hospitalization But Not Surgery
Time Frame	Time from start of study through year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Serious Adverse Events (Grades 3, 4, and 5) as Defined by CTCAE v3.0
Time Frame	Time from start of study through year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Secondary Outcome

Title	Overall Survival as Measured by Death From Any Cause
Time Frame	Time from start of study through year 5

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Adverse Event Reporting Description	Participants at Risk includes any patient who submitted an Adverse Event (AE) form.
Arm/Group Title	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
Arm/Group Description	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
All Cause Mortality
	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
	Affected / at Risk (%)	# Events
Total	1/89 (1.1%)
Gastrointestinal disorders
Diarrhea	1/89 (1.1%)
Other (Not Including Serious) Adverse Events
	Oxaliplatin + Leucovorin + 5-Fluorouracil + Bevacizumab
	Affected / at Risk (%)	# Events
Total	58/89 (65.2%)
Blood and lymphatic system disorders
Anemia	5/89 (5.6%)
Gastrointestinal disorders
Abdominal pain	6/89 (6.7%)
Diarrhea	7/89 (7.9%)
Nausea	6/89 (6.7%)
General disorders
Fatigue	14/89 (15.7%)
Immune system disorders
Anaphylaxis	9/89 (10.1%)
Investigations
Neutrophil count decreased	29/89 (32.6%)
White blood cell decreased	6/89 (6.7%)
Metabolism and nutrition disorders
Anorexia	5/89 (5.6%)
Dehydration	7/89 (7.9%)
Nervous system disorders
Peripheral sensory neuropathy	14/89 (15.7%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	8/89 (9%)
Vascular disorders
Thromboembolic event	10/89 (11.2%)

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.