Irinotecan and Celecoxib in Treating Patients With Unresectable or Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Giving irinotecan with celecoxib may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of irinotecan when given with celecoxib in treating patients with unresectable or metastatic colorectal cancer.

Detailed Description
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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.

Official Title
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A Phase I Study of Irinotecan in Combination With Fixed Dose Celecoxib in Patients With Advanced Colorectal Cancer

Conditions
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Colorectal Cancer, Diarrhea

Intervention / Treatment
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* Drug: celecoxib
* Drug: irinotecan hydrochloride


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|nan|
|Drug: irinotecan hydrochloride|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diarrhea, recurrent colon cancer, stage IV colon cancer, recurrent rectal cancer, stage IV rectal cancer, stage III colon cancer, stage III rectal cancer