A Phase I Study of Irinotecan in Combination With Fixed Dose Celecoxib in Patients With Advanced Colorectal Cancer
Data Collection
Colonic Diseases+10
+ Diarrhea
+ Digestive System Diseases
Treatment Study
Summary
Study start date: March 1, 2005
Actual date on which the first participant was enrolled.OBJECTIVES: Primary * Determine the maximum tolerated dose of irinotecan when administered with celecoxib in patients with unresectable or metastatic colorectal cancer. Secondary * Determine the dose-limiting toxic effects and non-dose-limiting toxic effects of this regimen in these patients. * Determine the incidence and intensity of diarrhea and myelotoxicity in patients treated with this regimen. * Determine any responses in patients treated with this regimen. * Determine potential mechanisms for irinotecan-induced diarrhea and protective effects of celecoxib on diarrhea prevention in patients treated with this regimen. OUTLINE: This is a dose-escalation study of irinotecan. Patients are assigned to 1 of 2 treatment groups. * Group I: Patients receive a fixed dose of irinotecan IV over 90 minutes on days 1, 8, 15, and 22 and oral celecoxib twice daily on days 10-42. Courses repeat every 42 days in the absence of disease progression or unacceptable toxicity. * Group II: Patients receive irinotecan as in group I at escalating doses and oral celecoxib twice daily on days 0-42. Treatment continues as in group I. Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. PROJECTED ACCRUAL: A total of 18-30 patients (9 for group I, 9-21 for group II) will be accrued for this study within 1-2 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.2 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: * Histologically confirmed colorectal cancer * Metastatic or unresectable disease * Failed first-line or second-line therapy OR recurred after receiving fluorouracil-based adjuvant chemotherapy * No known brain metastases PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 OR * Karnofsky 60-100% Life expectancy * More than 12 weeks Hematopoietic * Absolute neutrophil count ≥ 1,500/mm\^3 * Platelet count ≥ 100,000/mm\^3 * WBC ≥ 3,000/mm\^3 Hepatic * AST and ALT ≤ 2.5 times upper limit of normal * Bilirubin normal * No Gilbert's disease Renal * Creatinine normal OR * Creatinine clearance ≥ 60 mL/min Cardiovascular * No symptomatic congestive heart failure * No unstable angina pectoris * No cardiac arrhythmia Gastrointestinal * Able to receive oral medications * No prior inflammatory bowel disease * No active ulcer disease or gastritis * No contraindications for sigmoidoscopy * No active colostomy Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after study participation * No prior allergic reaction to compounds of similar chemical or biological composition to irinotecan, celecoxib, sulfonamides, or other study agents * No active or ongoing infection * No other concurrent uncontrolled illness * No psychiatric illness or social situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy * No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) Chemotherapy * See Disease Characteristics * No more than 2 prior different chemotherapy regimens, including adjuvant therapy * More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered * No prior irinotecan Endocrine therapy * Not specified Radiotherapy * More than 4 weeks since prior radiotherapy and recovered * No prior radiotherapy of more than 3,000 cGy * No prior radiotherapy to extended marrow-generating fields * No prior abdomino-pelvic irradiation Surgery * No prior abdominoperineal resection Other * More than 2 weeks since prior cyclo-oxygenase-2 (COX-2) inhibitors * No concurrent combination antiretroviral therapy for HIV-positive patients * No other concurrent investigational agents * No other anticancer therapy * No other concurrent COX-2 inhibitors * Low-dose aspirin allowed
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location