The Diarrhea Prevention with an investigational drug trial, will evaluate whether adding an investigational drug to the standard treatment for advanced colorectal cancer can reduce the amount of diarrhea a patient experiences. The standard and approved treatment for patients with metastatic colorectal cancer is repeated cycles of chemotherapy consisting of a combination of irinotecan (also known as CPT-11, Camptosar), 5-fluorouracil (also known as 5FU), and leucovorin (also known as LV). Preclinical data from animal models suggest that the investigational drug may offer an effective means for preventing CPT-11/5FU/LV-induced diarrhea. It is also hypothesized that the investigational drug-mediated anti-angiogenesis could induce a favorable tumor response.

Inclusion Criteria:

• Diagnosis of colorectal cancer (either newly diagnosed or recurrent disease) with evidence of metastatic disease and present or past histological documentation of adenocarcinoma of the colon or rectum.
• Tumor must be measureable.
• Resolution of all acute toxic effects of any prior radiotherapy or surgical procedure.
• ECOG performance status 0 or 1. Age >= 18 years.
• Required baseline laboratory.
• Negative pregnancy test.
• Willingness and ability to comply with the treatment plan.

Exclusion Criteria:

• Current enrollment in another clinical trial.
• Prior adjuvant therapy for colorectal cancer <= 6 months prior to randomization.
• Prior systemic anticancer therapy or intra-arterial cytotoxic chemotherapy given as treatment for metastatic colorectal cancer.
• Known allergy to CPT-11, 5-FU, LV, celecoxib, other COX-2 inhibitors, non-steroidal anti-inflammatory drugs (NSAIDS), salicylates, or sulfonamides.
• Chronic concomitant use of full-dose aspirin, other NSAIDs or other COX-2 inhibitors for a chronic nonmalignant condition.
• A requirement for chronic concomitant use of low-dose (cardioprotective) aspirin.
• Chronic oral steroid use for treatment of a non-malignant condition.
• Known ulceration of the gastric or duodenal mucosa <= 30 days prior to randomization.
• Need for concomitant fluconazole or lithium.
• Any known significant bleeding disorder.
• Active inflammatory bowel disease or chronic diarrhea.