A Phase I Study of Irinotecan in Combination With Fixed Dose Celecoxib in Patients With Advanced Colorectal Cancer
18 Years
N/A
Both
Colorectal Cancer, Diarrhea
Trial Information
A Phase I Study of Irinotecan in Combination With Fixed Dose Celecoxib in Patients With Advanced Colorectal Cancer
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Marwan Fakih, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Roswell Park Cancer Institute
Authority:
United States: Federal Government
Study ID:
RP 02-24
NCT ID:
NCT00084721
Start Date:
March 2005
Completion Date:
Related Keywords:
- Colorectal Cancer
- Diarrhea
- diarrhea
- recurrent colon cancer
- stage IV colon cancer
- recurrent rectal cancer
- stage IV rectal cancer
- stage III colon cancer
- stage III rectal cancer
- Colorectal Neoplasms
- Diarrhea
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
