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

Phase 1
18 Years
Not Enrolling
Colorectal Cancer, Diarrhea

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Trial Information

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



- Determine the maximum tolerated dose of irinotecan when administered with celecoxib in
patients with unresectable or metastatic colorectal cancer.


- 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


- 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



- 18 and over

Performance status

- ECOG 0-2 OR

- Karnofsky 60-100%

Life expectancy

- More than 12 weeks


- Absolute neutrophil count ≥ 1,500/mm^3

- Platelet count ≥ 100,000/mm^3

- WBC ≥ 3,000/mm^3


- AST and ALT ≤ 2.5 times upper limit of normal

- Bilirubin normal

- No Gilbert's disease


- Creatinine normal OR

- Creatinine clearance ≥ 60 mL/min


- No symptomatic congestive heart failure

- No unstable angina pectoris

- No cardiac arrhythmia


- Able to receive oral medications

- No prior inflammatory bowel disease

- No active ulcer disease or gastritis

- No contraindications for sigmoidoscopy

- No active colostomy


- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study

- 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


Biologic therapy

- No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF)


- 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


- 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


- No prior abdominoperineal resection


- 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:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Marwan Fakih, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Federal Government

Study ID:

RP 02-24



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



Roswell Park Cancer Institute Buffalo, New York  14263