Know Cancer

forgot password

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

Phase 2
18 Years
Not Enrolling
Colorectal Cancer

Thank you

Trial Information

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



- 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.


- 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.

Inclusion Criteria


- 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

- No evidence of Central Nervous System (CNS) metastases

- No recurrent local or metastatic disease after prior adjuvant therapy

- No diagnosis of rectal carcinoma


- 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

- 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

- 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


- 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

- No concurrent halogenated antiviral agents

- No other concurrent investigational drugs

- No other concurrent antineoplastic agents

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Major Morbidity Related to the Intact Primary Tumor

Outcome 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.

Outcome Time Frame:

24 months

Safety Issue:


Principal Investigator

Norman Wolmark, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

NSABP Foundation, Inc.


United States: Federal Government

Study ID:




Start Date:

March 2006

Completion Date:

December 2012

Related Keywords:

  • Colorectal Cancer
  • adenocarcinoma of the colon
  • stage IV colon cancer
  • Colonic Neoplasms
  • Colorectal Neoplasms



CCOP - Wichita Wichita, Kansas  67214-3882
CCOP - Christiana Care Health Services Wilmington, Delaware  19899
CCOP - Metro-Minnesota Saint Louis Park, Minnesota  55416
Bronson Methodist Hospital Kalamazoo, Michigan  49007
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Borgess Medical Center Kalamazooaa, Michigan  49001
Fairview Ridges Hospital Burnsville, Minnesota  55337
Mercy and Unity Cancer Center at Mercy Hospital Coon Rapids, Minnesota  55433
Fairview Southdale Hospital Edina, Minnesota  55435
Mercy and Unity Cancer Center at Unity Hospital Fridley, Minnesota  55432
Hutchinson Area Health Care Hutchinson, Minnesota  55350
Meeker County Memorial Hospital Lichfield, Minnesota  55355
Minnesota Oncology Hematology, PA - Maplewood Maplewood, Minnesota  55109
HealthEast Cancer Care at St. John's Hospital Maplewood, Minnesota  55109
Hennepin County Medical Center - Minneapolis Minneapolis, Minnesota  55415
Virginia Piper Cancer Institute at Abbott - Northwestern Hospital Minneapolis, Minnesota  55407
Hubert H. Humphrey Cancer Center at North Memorial Outpatient Center Robbinsdale, Minnesota  55422-2900
St. Francis Cancer Center at St. Francis Medical Center Shakopee, Minnesota  55379
Park Nicollet Cancer Center St. Louis Park, Minnesota  55416
Regions Hospital Cancer Care Center St. Paul, Minnesota  55101
United Hospital St. Paul, Minnesota  55102
Ridgeview Medical Center Waconia, Minnesota  55387
Minnesota Oncology Hematology, PA - Woodbury Woodbury, Minnesota  55125
Aultman Cancer Center at Aultman Hospital Canton, Ohio  44710-1799
Sanford Cancer Center at Sanford USD Medical Center Sioux Falls, South Dakota  57117-5039
Medical X-Ray Center, PC Sioux Falls, South Dakota  57105
Avera Cancer Institute Sioux Falls, South Dakota  57105
Marshfield Clinic - Marshfield Center Marshfield, Wisconsin  54449
Memorial Hospital of South Bend South Bend, Indiana  46601
CCOP - Cancer Research for the Ozarks Springfield, Missouri  65807
CCOP - Montana Cancer Consortium Billings, Montana  59101
CCOP - Columbus Columbus, Ohio  43206
Veterans Affairs Medical Center - Dayton Dayton, Ohio  45428
CCOP - Dayton Kettering, Ohio  45429
CCOP - Greenville Greenville, South Carolina  29615
Joe Arrington Cancer Research and Treatment Center Lubbock, Texas  79410-1894
CCOP - Northern Indiana CR Consortium South Bend, Indiana  46601
Saint Joseph Regional Medical Center South Bend, Indiana  46617
Holden Comprehensive Cancer Center at University of Iowa Iowa City, Iowa  52242-1002
Kimmel Cancer Center at Thomas Jefferson University - Philadelphia Philadelphia, Pennsylvania  19107
Kaiser Permanente Medical Center - Vallejo Vallejo, California  94589
City of Hope Comprehensive Cancer Center Duarte, California  91010
Fletcher Allen Health Care - University Health Center Campus Burlington, Vermont  05401
Kaiser Permanente Medical Center - San Francisco Geary Campus San Francisco, California  94115
Arkansas Cancer Research Center at University of Arkansas for Medical Sciences Little Rock, Arkansas  72205
Josephine Ford Cancer Center at Henry Ford Hospital Detroit, Michigan  48202
Hulston Cancer Center at Cox Medical Center South Springfield, Missouri  65807
St. John's Regional Health Center Springfield, Missouri  65804
McDowell Cancer Center at Akron General Medical Center Akron, Ohio  44307
Kaiser Permanente Medical Center - Oakland Sacramento, California  95825
Via Christi Cancer Center at Via Christi Regional Medical Center Wichita, Kansas  67214
Wake Forest University Comprehensive Cancer Center Winston-Salem, North Carolina  27157-1096
McCreery Cancer Center at Ottumwa Regional Ottumwa, Iowa  52501
CCOP - Hematology-Oncology Associates of Central New York East Syracuse, New York  13057
Mount Nittany Medical Center State College, Pennsylvania  16803
Sibley Memorial Hospital Washington, District of Columbia  20016
Southwest Medical Center Liberal, Kansas  67901
Northern Rockies Radiation Oncology Center Billings, Montana  59101
Hematology-Oncology Centers of the Northern Rockies - Billings Billings, Montana  59101
Kalispell Regional Medical Center Kalispell, Montana  59901
Glacier Oncology, PLLC Kalispell, Montana  59901
Montana Cancer Center at St. Patrick Hospital and Health Sciences Center Missoula, Montana  59802
Montana Cancer Specialists at Montana Cancer Center Missoula, Montana  59802
Community Medical Center Missoula, Montana  59801
Wayne Memorial Hospital, Incorporated Goldsboro, North Carolina  27534
Adena Regional Medical Center Chillicothe, Ohio  54601
Doctors Hospital at Ohio Health Columbus, Ohio  43228
Riverside Methodist Hospital Cancer Care Columbus, Ohio  43214
Grady Memorial Hospital Delaware, Ohio  43015
Fairfield Medical Center Lancaster, Ohio  43130
Strecker Cancer Center at Marietta Memorial Hospital Marietta, Ohio  45750
Licking Memorial Cancer Care Program at Licking Memorial Hospital Newark, Ohio  43055
Community Hospital of Springfield and Clark County Springfield, Ohio  45505
Genesis - Good Samaritan Hospital Zanesville, Ohio  43701
Kaiser Permanente Medical Center - Santa Clara Kiely Campus Santa Clara, California  95051-5386
Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center Savannah, Georgia  31403-3089
Advocate Lutheran General Cancer Care Center Park Ridge, Illinois  60068-1174
St. Barnabas Medical Center Cancer Center Livingston, New Jersey  07039
West Virginia University Health Sciences Center - Charleston Charleston, West Virginia  25302
Kaiser Permanente Medical Center - Sacramento Sacramento, California  95825
Methodist Estabrook Cancer Center Omaha, Nebraska  68114-4199
Decatur Memorial Hospital Cancer Care Institute Decatur, Illinois  62526
Elkhart General Hospital Elkhart, Indiana  46515
Howard Community Hospital Kokomo, Indiana  46904
Harry & Jeanette Weinberg Cancer Institute at Franklin Square Hospital Center Baltimore, Maryland  21237
Lakeland Regional Cancer Care Center - St. Joseph St. Joseph, Michigan  49085
Mount Carmel Health - West Hospital Columbus, Ohio  43222
Lakeland Regional Cancer Center at Lakeland Regional Medical Center Lakeland, Florida  33805
Kaiser Permanente - Fremont Fremont, California  94538
Kaiser Permanente Medical Center - Hayward Hayward, California  94545
Kaiser Permanente Medical Center - Redwood City Redwood City, California  94063
Kaiser Permanente Medical Center - Richmond Richmond, California  94801
Kaiser Permanente Medical Center - Roseville Roseville, California  95661
South Sacramento Kaiser-Permanente Medical Center Sacramento, California  95823
Kaiser Permanente Medical Office -Vandever Medical Office San Diego, California  92120
Kaiser Permanente Medical Center - Santa Teresa San Jose, California  95119
Kaiser Foundation Hospital - San Rafael San Rafael, California  94903
Kaiser Permanente Medical Center - Santa Rosa Santa Rosa, California  95403
Kaiser Permanente Medical Center - South San Francisco South San Francisco, California  94080
Kaiser Permanente Medical Facility - Stockton Stockton, California  95210
Kaiser Permanente Medical Center - Walnut Creek Walnut Creek, California  94596
St. Francis Hospital and Health Centers - Beech Grove Campus Beech Grove, Indiana  46107
Center for Cancer Therapy at LaPorte Hospital and Health Services La Porte, Indiana  46350
Cancer Center of Kansas, PA - Dodge City Dodge City, Kansas  67801
Cancer Institute of New Jersey at Cooper - Voorhees Voorhees, New Jersey  08043
Charles R. Wood Cancer Center at Glens Falls Hospital Glens Falls, New York  12801
Samaritan North Cancer Care Center Dayton, Ohio  45415
Grandview Hospital Dayton, Ohio  45405
David L. Rike Cancer Center at Miami Valley Hospital Dayton, Ohio  45409
Good Samaritan Hospital Dayton, Ohio  45406
Blanchard Valley Medical Associates Findlay, Ohio  45840
Charles F. Kettering Memorial Hospital Kettering, Ohio  45429
Middletown Regional Hospital Middletown, Ohio  45044
Mercy Medical Center Springfield, Ohio  45504
UVMC Cancer Care Center at Upper Valley Medical Center Troy, Ohio  45373-1300
Ruth G. McMillan Cancer Center at Greene Memorial Hospital Xenia, Ohio  45385
Bryn Mawr Hospital Bryn Mawr, Pennsylvania  19010
Lankenau Cancer Center at Lankenau Hospital Wynnewood, Pennsylvania  19096
Danville Regional Medical Center Danville, Virginia  24541
Missouri Baptist Cancer Center St. Louis, Missouri  63131
Allegheny Cancer Center at Allegheny General Hospital Pittsburgh, Pennsylvania  15212
Tunnell Cancer Center at Beebe Medical Center Lewes, Delaware  19958
Reid Hospital & Health Care Services Richmond, Indiana  47374
McFarland Clinic, PC Ames, Iowa  50010
Cancer Center of Kansas, PA - Chanute Chanute, Kansas  66720
Cancer Center of Kansas, PA - El Dorado El Dorado, Kansas  67042
Cancer Center of Kansas, PA - Kingman Kingman, Kansas  67068
Lawrence Memorial Hospital Lawrence, Kansas  66044
Cancer Center of Kansas, PA - Newton Newton, Kansas  67114
Cancer Center of Kansas, PA - Parsons Parsons, Kansas  67357
Cancer Center of Kansas, PA - Pratt Pratt, Kansas  67124
Cancer Center of Kansas, PA - Salina Salina, Kansas  67401
Cancer Center of Kansas, PA - Wellington Wellington, Kansas  67152
Cancer Center of Kansas, PA - Wichita Wichita, Kansas  67214
Associates in Womens Health, PA - North Review Wichita, Kansas  67208
Cancer Center of Kansas, PA - Medical Arts Tower Wichita, Kansas  67208
Cancer Center of Kansas, PA - Winfield Winfield, Kansas  67156
Union Hospital Cancer Program at Union Hospital Elkton MD, Maryland  21921
Arch Medical Services, Incorporated at Center for Cancer Care and Research Saint Louis, Missouri  63141
St. James Healthcare Cancer Care Butte, Montana  59701
Great Falls Clinic - Main Facility Great Falls, Montana  59405
Kalispell Medical Oncology at KRMC Kalispell, Montana  59901
Mary Rutan Hospital Bellefontaine, Ohio  43311
Grant Medical Center Cancer Care Columbus, Ohio  43215
Wayne Hospital Greenville, Ohio  45331
Mount Carmel St. Ann's Cancer Center Westerville, Ohio  43081
Clinton Memorial Hospital Wilmington, Ohio  45177
Hematology and Oncology Associates of Northeastern Pennsylvania Scranton, Pennsylvania  18510
Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital Parkersburg, West Virginia  26102
Regional Cancer Center at Memorial Medical Center Springfield, Illinois  62781-0001
John H. Stroger, Jr. Hospital of Cook County Chicago, Illinois  60612-9985
Great Falls, Montana  59405
Guardian Oncology and Center for Wellness Missoula, Montana  59804
Louisville Oncology at Norton Cancer Institute - Louisville Louisville, Kentucky  40202
Scripps Cancer Center - San Diego San Diego, California  92121
St. Vincent Healthcare Cancer Care Services Billings, Montana  59101
Riddle Memorial Hospital Cancer Center Media, Pennsylvania  19063
Cancer Center of Paoli Memorial Hospital Paoli, Pennsylvania  19301-1792
CCOP - Main Line Health Wynnewood, Pennsylvania  19096
Associates in Hematology-Oncology, PC at Crozer Regional Cancer Center Upland, Pennsylvania  19013
Hudner Oncology Center at Saint Anne's Hospital - Fall River Fall River, Massachusetts  02721
Cancer Institute at St. Joseph Medical Center Towson, Maryland  21204
Oncology Hematology Care, Incorporated - Blue Ash Cincinnati, Ohio  45242