Clinical trial NCT00037180: For Prevention of Diarrhea in Patients Diagnosed With Metastatic Colorectal Cancer Treated With Chemotherapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neoplasm Metastasis
Colorectal Neoplasms
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2002-05-17
Enrollment: 212
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of NCI CTC grade 2-4 diarrhea during the first cycle (6 weeks) of CPT-11/5-FU/LV chemotherapy
Secondary outcomes:
measure: Severity of all grades of diarrhea, overall and by cycle
measure: Duration of diarrhea, by cycle
measure: Diarrhea grade, by day, by cycle
measure: Stool count, by day, by cycle
measure: Severity of asthenia (fatigue), by week.
measure: Asthenia will be assessed with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) scale.
measure: Duration of asthenia, by week, as measured by the FACIT-Fatigue scale
measure: 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
measure: Compliance with celecoxib use Incidence, quantity, and duration of loperamide use
measure: Tumor response rate (overall and confirmed)using the World Health Organization [WHO] Response Evaluation Criteria in Solid Tumors [RECIST 2000]
measure: Serum tumor marker (carcinoembryonic antigen [CEA]) response rate (as characterized by a 50% reduction from baseline)
measure: Time to tumor progression (TTP)
measure: Time to treatment failure (TTF)
measure: Survival Post-study anticancer treatment
measure: 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)
measure: Inflammatory cytokines which may serve as biomarkers for cancer-related outcomes Beta-glucuronidase as a potential biomarker for tumor response
measure: Health resource utilization (collected data to be evaluated separately from this protocol)
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Pfizer Investigational Site
state: Alabama
city: Ft. Lauderdale
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Port St. Lucie
country: United States
facility: Pfizer Investigational Site
state: Florida
city: Chicago
country: United States
facility: Pfizer Investigational Site
state: Illinois
city: St. Joseph
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: St. Louis
country: United States
facility: Pfizer Investigational Site
state: Missouri
city: Buffalo
country: United States
facility: Pfizer Investigational Site
state: New York
city: Williamsville
country: United States
facility: Pfizer Investigational Site
state: New York
city: Altoona
country: United States
facility: Pfizer Investigational Site
state: Pennsylvania
city: Puyallup
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Yakima
country: United States
facility: Pfizer Investigational Site
state: Washington
city: Milwaukee
country: United States
facility: Pfizer Investigational Site
state: Wisconsin
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: