For Prevention of Diarrhea in Patients Diagnosed With Metastatic Colorectal Cancer Treated With Chemotherapy

Phase II, Randomized, Double-Blind, Multicenter Trial Of Celecoxib Vs Placebo For The Prevention Of Diarrhea Associated With CPT-11/5fu/LV Chemotherapy In Patients With Previously Untreated Metastatic Colorectal Cancer

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.

Study Overview

• Status: Terminated
• Conditions: Neoplasm Metastasis; Colorectal Neoplasms
• Intervention / Treatment: Drug: Leucovorin; Drug: Celecoxib; Drug: 5-fluorouracil; Drug: Irinotecan

• Study Type: Interventional
• Enrollment: 212
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36685
      • Pfizer Investigational Site
  • Florida
    • Ft. Lauderdale, Florida, United States, 33308
      • Pfizer Investigational Site
    • Port St. Lucie, Florida, United States, 34952
      • Pfizer Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60631
      • Pfizer Investigational Site
  • Missouri
    • St. Joseph, Missouri, United States, 64507
      • Pfizer Investigational Site
    • St. Louis, Missouri, United States, 63136
      • Pfizer Investigational Site
  • New York
    • Buffalo, New York, United States, 14215
      • Pfizer Investigational Site
    • Williamsville, New York, United States, 14221
      • Pfizer Investigational Site
  • Pennsylvania
    • Altoona, Pennsylvania, United States, 16601
      • Pfizer Investigational Site
  • Washington
    • Puyallup, Washington, United States, 98372
      • Pfizer Investigational Site
    • Yakima, Washington, United States, 98902
      • Pfizer Investigational Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Pfizer Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Incidence of NCI CTC grade 2-4 diarrhea during the first cycle (6 weeks) of CPT-11/5-FU/LV chemotherapy

Secondary Outcome Measures

Outcome Measure
Time to treatment failure (TTF)
Time to tumor progression (TTP)
Severity of all grades of diarrhea, overall and by cycle
Duration of diarrhea, by cycle
Diarrhea grade, by day, by cycle
Stool count, by day, by cycle
Severity of asthenia (fatigue), by week.
Asthenia will be assessed with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale.
Duration of asthenia, by week, as measured by the FACIT-Fatigue scale
Type, frequency, severity, timing, and relatedness of all adverse events CPT-11/5-FU/LV treatment administration as characterized by median, mean, and range of doses given; dose modifications, omissions, and delays; and actual and relative dose intensity
Compliance with celecoxib use Incidence, quantity, and duration of loperamide use
Tumor response rate (overall and confirmed)using the World Health Organization [WHO] Response Evaluation Criteria in Solid Tumors [RECIST 2000]
Serum tumor marker (carcinoembryonic antigen [CEA]) response rate (as characterized by a 50% reduction from baseline)
Survival Post-study anticancer treatment
Peak plasma levels and AUC 0-24 values for CPT-11 and its major metabolites, SN-38, SN-38 glucuronide (SN-38G), and aminopentane carboxylic acid (APC)
Inflammatory cytokines which may serve as biomarkers for cancer-related outcomes Beta-glucuronidase as a potential biomarker for tumor response
Health resource utilization (collected data to be evaluated separately from this protocol)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start: April 1, 2002
• Study Completion (Actual): January 1, 2003

Study Registration Dates

• First Submitted: May 16, 2002
• First Submitted That Met QC Criteria: May 16, 2002
• First Posted (Estimate): May 17, 2002

Study Record Updates

• Last Update Posted (Estimate): September 29, 2008
• Last Update Submitted That Met QC Criteria: September 25, 2008
• Last Verified: September 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms by Site; Signs and Symptoms, Digestive; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Neoplasms; Colorectal Neoplasms; Neoplasm Metastasis; Diarrhea; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Topoisomerase Inhibitors; Micronutrients; Vitamins; Cyclooxygenase 2 Inhibitors; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Fluorouracil; Celecoxib; Leucovorin; Irinotecan
• Other Study ID Numbers: IQ8-01-02-016