In This SectionTexas Health Research & Education Institute
Disease or Condition
TRIAL COMPARING INFUSIONAL 5-FLUOROURACIL, LEUCOVORIN, AND OXALIPLATIN EVERY TWO WEEKS WITH BEVACIZUMAB TO THE SAME REGIMEN WITHOUT BEVACIZUMAB FOR THE TREATMENT OF PATIENTS WITH RESECTED STAGE II AND III CARCINOMA OF THE COLON (Colon Cancer)
The purpose of this study is to compare the effects from a combination of chemotherapy drugs given with and without a new drug call bevacizumab to see if the addition of this new drug is better for treating colon cancer and decreases the cancer from reoccuring.
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.
Patients must be = 18 years old.
Randomization must occur during the three-week interval beginning onpostoperative 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:
a. 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).
b. Stage III carcinoma (any T N1,2 M0) The tumor has invaded to any depth, with involvement of regional lymph nodes.Appendix A provides TNM nomenclature and staging for colon cancer.
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:
a .all or a portion of the adjacent structure was removed en bloc with the primary tumor.
b. in the opinion of the surgeon, all grossly visible tumor was completely resected ("curative resection").
c. histologic evaluation by the pathologist confirms the margins of the resected specimen are not involved by malignant cells; and
d. 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).
In the opinion of the investigator, patients must have a life expectancy of at least 5 years, excluding their diagnosis of cancer.
Patients must have an ECOG performance status of 0 or 1. (See Appendix B.).
At the time of randomization, postoperative absolute granulocyte count (AGC) must be = 1500/mm3 (or < 1500/mm3, 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/mm3.
There must be postoperative evidence of adequate hepatic function.
a. 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.
b. Alkaline phosphatase must be < 2.5 x ULN for the lab. • ASTmustbe<1.5xULNforthelab.
If AST is > ULN, serologic testing for Hepatitis B and C must be performed and results must be negative.
There must be postoperative evidence of adequate renal function.
c. 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 (see Appendix G).
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 recurrenc.
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.
Patients less than 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 fracture87. Gastroduodenal ulcer(s) determined by endoscopy to be active.
Invasive procedures defined as follows:
a. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization.
b. 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 rndomization.
Uncontrolled blood pressure defined as > 150/90 mmHg.
History of TIA or CV A.
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:
a. 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:
a. New York Heart Association Class III or IV cardiac disease.
b. History of myocardial infarction within 12 months before study entry.
c. Unstable angina within 12 months before study entry.
d. 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.