Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II or Stage III Colon Cancer

Not Recruiting

Trial ID: NCT00096278


This randomized phase III trial is studying giving oxaliplatin, leucovorin, and fluorouracil together with bevacizumab to see how well it works compared to oxaliplatin, leucovorin, and fluorouracil alone in treating patients who have undergone surgery for stage II or stage III colon cancer. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as bevacizumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Bevacizumab may also stop the growth of tumor cells by stopping blood flow to the tumor. Giving chemotherapy together with bevacizumab may kill more tumor cells. It is not yet known whether treatment with oxaliplatin, leucovorin, and fluorouracil is more effective with or without bevacizumab in treating patients who have undergone surgery for colon cancer.

Official Title

A Phase III Clinical Trial Comparing Infusional 5-Fluorouracil (5-FU), Leucovorin, and Oxaliplatin (mFOLFOX6) Every Two Weeks With Bevacizumab to the Same Regimen Without Bevacizumab for the Treatment of Patients With Resected Stages II and III Carcinoma of the Colon

Stanford Investigator(s)

Andrew A. Shelton, MD, FACS, FACRS
Andrew A. Shelton, MD, FACS, FACRS

Clinical Professor, Surgery - General Surgery

George A. Fisher Jr.
George A. Fisher Jr.

Colleen Haas Chair in the School of Medicine


Inclusion Criteria:

   - Patients must consent to be in the study and must have signed and dated an IRB
   approved consent form conforming to federal and institutional guidelines

   - Randomization must occur during the three-week interval beginning on postoperative day
   29 and ending on postoperative day 50

   - The distal extent of the tumor must be >= 12 cm from the anal verge on endoscopy; if
   the patient is not a candidate for endoscopy, then the distal extent of the tumor must
   be >= 12 cm from the anal verge as determined by surgical examination

   - The patient must have had an en bloc complete gross resection of tumor (curative
   resection) by open laparotomy or laparoscopically-assisted colectomy; patients who
   have had a two-stage surgical procedure, to first provide a decompressive colostomy
   and then in a later procedure to have the definitive surgical resection, are eligible

   - Patients must have histologically confirmed adenocarcinoma of the colon that meets one
   of the criteria below:

      - Stage II carcinoma (T3,4 N0 M0); the tumor invades through the muscularis propria
      into the subserosa or into non-peritonealized pericolic or perirectal tissues
      (T3); or directly invades other organs or structures, and/or perforates visceral
      peritoneum (T4)

      - Stage III carcinoma (any T N1,2 M0); the tumor has invaded to any depth, with
      involvement of regional lymph nodes

   - Patients with T4 tumors that have involved an adjacent structure (e.g., bladder, small
   intestine, ovary, etc.) by direct extension from the primary tumor are eligible if all
   of the following conditions are met:

      - All or a portion of the adjacent structure was removed en bloc with the primary

      - In the opinion of the surgeon, all grossly visible tumor was completely resected
      ("curative resection")

      - Histologic evaluation by the pathologist confirms the margins of the resected
      specimen are not involved by malignant cells; and

      - Local radiation therapy will not be utilized

   - Patients with more than one synchronous primary colon tumor are eligible; (staging
   classification will be based on the more advanced primary tumor)

   - Patients must have an ECOG performance status of 0 or 1

   - At the time of randomization, postoperative absolute granulocyte count (AGC) must be
   >= 1500/mm^3 (or < 1500/mm^3, if in the opinion of the investigator, this represents
   an ethnic or racial variation of normal)

   - At the time of randomization, the postoperative platelet count must be >= 100,000/mm^3

   - Bilirubin must be =< ULN for the lab unless the patient has a chronic grade 1
   bilirubin elevation due to Gilbert's disease or similar syndrome due to slow
   conjugation of bilirubin

   - Alkaline phosphatase must be < 2.5 x ULN for the lab

   - AST must be < 1.5 x ULN for the lab

      - If AST is > ULN, serologic testing for hepatitis B and C must be performed and
      results must be negative

   - Serum creatinine =< 1.5 x ULN for the lab

   - Urine protein/creatinine (UPC) ratio of < 1.0; patients with a UPC ratio >= 1.0 must
   undergo a 24-hour urine collection, which must be an adequate collection and must
   demonstrate < 1 gm of protein in the 24-hour urine collection in order to participate
   in the study

   - Patients with prior malignancies, including colorectal cancers, are eligible if they
   have been disease-free for >= 5 years and are deemed by their physician to be at low
   risk for recurrence; patients with squamous or basal cell carcinoma of the skin,
   melanoma in situ, carcinoma in situ of the cervix, or carcinoma in situ of the colon
   or rectum that have been effectively treated are eligible, even if these conditions
   were diagnosed within 5 years prior to randomization

Exclusion Criteria:

   - Patients < 18 years old

   - Colon tumor other than adenocarcinoma, i.e., sarcoma, lymphoma, carcinoid, etc

   - Rectal tumors, i.e. a tumor located < 12 cm from the anal verge on endoscopy, or by
   surgical exam if the patient is not a candidate for endoscopy

   - Isolated, distant, or non-contiguous intra-abdominal metastases, even if resected

   - Any systemic or radiation therapy initiated for this malignancy

   - Any significant bleeding that is not related to the primary colon tumor within 6
   months before study entry

   - Serious or non-healing wound, skin ulcers, or bone fracture

   - Gastroduodenal ulcer(s) determined by endoscopy to be active

   - Invasive procedures defined as follows:

      - Major surgical procedure, open biopsy, or significant traumatic injury within 28
      days prior to randomization

      - Anticipation of need for major surgical procedures during the course of the study

      - Core biopsy or other minor procedure, excluding placement of a vascular access
      device, within 7 days prior to randomization

   - Uncontrolled blood pressure defined as > 150/90 mmHg

   - History of TIA or CVA

   - History of arterial thrombotic event within 12 months before study entry

   - Symptomatic peripheral vascular disease

   - PT/INR > 1.5, unless the patient is on therapeutic doses of warfarin. If so, the
   following criteria must be met for enrollment:

      - The subject must have an in-range INR (usually between 2 and 3) on a stable dose
      of warfarin

      - The subject must not have active bleeding or a pathological condition that is
      associated with a high-risk of bleeding

   - Concomitant halogenated antiviral agents

   - Clinically significant peripheral neuropathy at the time of randomization (defined in
   the NCI Common Terminology Criteria for Adverse Events Version 3.0 [CTCAE v3.0] as
   grade 2 or greater neurosensory or neuromotor toxicity)

   - Non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that would
   preclude any of the study therapy drugs; specifically excluded are the following
   cardiac conditions:

      - New York Heart Association Class III or IV cardiac disease

      - History of myocardial infarction within 12 months before study entry

      - Unstable angina within 12 months before study entry; and

      - Symptomatic arrhythmia

   - History of chronic or persistent viral hepatitis or other chronic liver disease

   - Pregnancy or lactation at the time of proposed randomization; eligible patients of
   reproductive potential (both sexes) must agree to use adequate contraceptive methods
   during study therapy and for at least 3 months after the completion of bevacizumab

   - Psychiatric or addictive disorders or other conditions that, in the opinion of the
   investigator, would preclude the patient from meeting the study requirements


drug: leucovorin calcium

drug: fluorouracil

biological: bevacizumab

drug: oxaliplatin

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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