The purpose of this study is to determine: 1. What method of treatment is more effective: infusional or optimized bolus schedule; 2. Whether Camptosar, Avastin (added in April 2004) and 5-FU/Leucovorin are safe to treat metastatic colorectal cancer patients; 3. Whether Celebrex may improve safety and/or effectiveness of the treatment.

*The study was modified in April 2004 to discontinue a 3rd treatment schedule containing Xeloda, and Avastin was added to the remaining schedules.

Condition	Treatment or Intervention	Phase
Colorectal Cancer Metastases	Drug: 5-Fluorouracil  Drug: Bevacizumab  Drug: Celecoxib  Drug: Irinotecan  Drug: Leucovorin  Drug: Capecitabine	Phase III

Further Study Details: 

Primary Outcomes: To compare the time to progression of irinotecan in combination with infusional 5-FU/LV (FOLFIRI), and modified-bolus 5-FU/LV (Day 1 & 8) as first-line treatment of patients with metastatic colorectal cancer.
Secondary Outcomes: To compare the two different irinotecan combination regimens (infusional 5-FU and modified-bolus 5-FU) for effect on survival and safety; To compare celecoxib vs. placebo for effect on time to progression, survival and safety; To compare celecoxib vs. placebo for effect on time to progression, survival and safety among patients who received concomitant bevacizumab; To compare the two different irinotecan combination regimens (infusional 5-FU vs modified-bolus 5-FU) among patients who received concomitant bevacizumab for effect on time to progression, survival and safety; Exploratory comparisons will be made between arm C and arms A and B for subjects enrolled before Amendment 2
Expected Total Enrollment:  1200

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

• Metastatic adenocarcinoma of the colon or rectum with at least one measurable lesion
• 12 months from the last treatment dose of adjuvant therapy
• ECOG performance status of 0 or 1
• Resolution of all acute toxic effects of any prior radiotherapy
• Must have completed major surgery more than 4 weeks ago
• Adequate hematologic, hepatic and renal function
• No COX-2 inhibitors and NSAIDs (low-dose ASA permitted)
• Urine protein < 1 mg/dL
• No prior systemic anticancer therapy for metastatic colorectal cancer or concurrent anticancer therapy
• No concurrent malignancies
• No leptomeningeal disease
• No known ulceration of gastric or duodenal mucosa within 30 days, uncontrolled predisposing colonic or small bowel disorders, partial or complete bowel obstruction, known chronic malabsorption, total colectomy or other major abdominal surgery that may result in substantial malabsorption
• No inadequately controlled hypertension - BP > 160/100 on medication, unstable angina, MI, CVA, TIA, PE, DVT, significant thromboembolic event, uncontrolled ventricular cardiac arrhythmias, symptomatic CHF, symptomatic CAD, uncontrolled diabetes mellitus or infection or other serious underlying medical condition
• No chronic steroid use
• No prior therapy with irinotecan, topotecan or bevacizumab
• No enzyme-inducing anti-convulsant or St. John's wort use
• No concomitant fluconazole at study entry
• No allergy to any of the study drugs, other COX-2 inhibitors, NSAIDs, salicilates or sorivudine

Study ID Numbers:  CPTAIV-0020-411
Record last reviewed:  January 2005
Last Updated:  January 12, 2005
Record first received:  January 12, 2005
ClinicalTrials.gov Identifier:  NCT00101686
Health Authority: United States: Institutional Review Board (Awaiting confirmation)
ClinicalTrials.gov processed this record on 2005-04-08