Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer

Sponsor

European Organisation for Research and Treatment of Cancer - EORTC (Other)

Overall Status

Completed

CT.gov ID

NCT00064181

Collaborator

(none)

Enrollment

Locations

3.1

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy such as irinotecan, capecitabine, leucovorin, and fluorouracil use different ways to stop tumor cells from dividing so they stop growing or die. Celecoxib may stop the growth of colorectal cancer by stopping blood flow to the tumor. It is not yet known which combination chemotherapy regimen with or without celecoxib is more effective in treating metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying two combination chemotherapy regimens and celecoxib to see how well they work compared to two combination chemotherapy regimens alone in treating patients with metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: FOLFIRI regimen Drug: capecitabine Drug: celecoxib Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium	Phase 3

Detailed Description

OBJECTIVES:

Compare the progression-free survival of patients with metastatic colorectal cancer treated with capecitabine and irinotecan vs fluorouracil, leucovorin calcium, and irinotecan with vs without celecoxib.
Compare the safety of these regimens in these patients.
Compare the response rate in patients treated with these regimens.
Compare the time to treatment failure and overall survival of patients treated with these regimens.

OUTLINE: This is a randomized, double-blind*, multicenter study. Patients are stratified according to participating center, prior adjuvant therapy (yes vs no), and risk group (poor vs intermediate vs good). Patients are randomized to 1 of 4 treatment arms.

Arm I: Patients receive irinotecan IV over 30-90 minutes on days 1 and 22; oral capecitabine twice daily on days 1-15 and 22-36; and oral celecoxib twice daily on days 1-42.
Arm II: Patients receive irinotecan and capecitabine as in arm I and oral placebo twice daily on days 1-42.
Arm III: Patients receive irinotecan IV over 30-90 minutes on days 1, 15, and 29; leucovorin calcium (CF) IV over 2 hours and fluorouracil (5-FU) IV over 22 hours on days 1, 2, 15, 16, 29, and 30; and oral celecoxib twice daily on days 1-42.
Arm IV: Patients receive irinotecan, CF, and 5-FU as in arm III and oral placebo twice daily on days 1-42.

In all arms, treatment repeats every 6 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. If all chemotherapy is discontinued due to toxicity, patients may continue celecoxib or placebo until disease progression, unacceptable toxicity, or starting a new cytotoxic regimen.

NOTE: *The double-blind treatment only applies to the celecoxib and placebo randomization

Patients are followed every 2 months.

PROJECTED ACCRUAL: A total of 692 patients (173 per treatment arm) will be accrued for this study within 3.5 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

86 participants

Allocation:

Randomized

Masking:

Double

Primary Purpose:

Treatment

Official Title:

Irinotecan Combined With Infusional 5-FU/Folinic Acid or Capecitabine and the Role of Celecoxib in Patients With Metastatic Colorectal Cancer

Study Start Date :

May 1, 2003

Actual Primary Completion Date :

Jan 1, 2005

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed adenocarcinoma of the colon or rectum
Metastatic disease
Measurable disease
Patients who received prior radiotherapy must have measurable or evaluable disease outside the radiotherapy field
No CNS metastases

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

WHO 0-2

Life expectancy

Not specified

Hematopoietic

WBC at least 3,000/mm^3
Platelet count at least 100,000/mm^3

Hepatic

Bilirubin no greater than 2 times upper limit of normal (ULN)
AST and ALT no greater than 2.5 times ULN (5 times ULN in the presence of liver metastases)

Renal

Creatinine clearance at least 51 mL/min
No severe renal impairment

Cardiovascular

No severe cardiac disease
No uncontrolled angina pectoris
No myocardial infarction within the past 6 months

Other

Not pregnant or nursing
Fertile patients must use effective contraception during and for 6 months after study participation
No active Crohn's disease
No other malignancy except adequately treated carcinoma in situ of the cervix or nonmelanoma skin cancer
No other uncontrolled severe medical condition
No psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent active or passive immunotherapy for colon cancer

Chemotherapy

No prior chemotherapy for metastatic disease

Endocrine therapy

Not specified

Radiotherapy

See Disease Characteristics
At least 4 weeks since prior radiotherapy
No concurrent radiotherapy

Surgery

Not specified

Other

At least 6 months since prior adjuvant therapy
More than 4 weeks since prior investigational drugs
No concurrent sorivudine or chemically related analogues (e.g., brivudine)
No other concurrent investigational drugs
No other concurrent cytotoxic agents
No concurrent prophylactic fluconazole
No concurrent or planned cyclo-oxygenase-2 (COX-2) inhibitors or nonsteroidal anti-inflammatory drugs
No concurrent chronic use of full-dose aspirin (325 mg/day or greater)
Concurrent low-dose (cardioprotective) aspirin prophylaxis (no more than 325 mg every other day OR no more than 162.5 mg per day) allowed

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Ziekenhuis Network Antwerpen Middelheim	Antwerp	Belgium	2020
2	Institut Jules Bordet	Brussels	Belgium	1000
3	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels	Belgium	1090
4	Universitair Ziekenhuis Antwerpen	Edegem	Belgium	B-2650
5	Cazk Groeninghe - Campus St-Niklaas	Kortrijk	Belgium	B-8500
6	St. Elizabeth Ziekenhuis	Turnhout	Belgium	2300
7	National Cancer Institute - Cairo	Cairo	Egypt
8	Charite - Campus Charite Mitte	Berlin	Germany	D-10117
9	General Hospital	Celle	Germany	29223
10	Universitatsklinikum Carl Gustav Carl Carus	Dresden	Germany	D-01307
11	Kliniken Essen - Mitte	Essen	Germany	D-45136
12	Klinikum der J.W. Goethe Universitaet	Frankfurt	Germany	D-60590
13	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg	Germany	D-79106
14	Allgemeines Krankenhaus Hagen	Hagen	Germany	D-58095
15	Allgemeines Krankenhaus Altona	Hamburg	Germany	22763
16	Universitaets-Krankenhaus Eppendorf	Hamburg	Germany	D-20246
17	St. Marien Hospital	Hamm	Germany	59065
18	Westpfalz-Klinikum GmbH	Kaiserslautern	Germany	D-67653
19	Vinzentiuskrankenhaus	Landau	Germany	D-76829
20	Onkologische Schwerpunktpraxis Leer	Leer	Germany	D-26789
21	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg	Germany	D-39120
22	Kreiskrankenhaus Meissen	Meissen	Germany	D-01662
23	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich	Germany	D-81675
24	Eberhard Karls Universitaet	Tuebingen	Germany	D-72076
25	Universitaets-Hautklinik Wuerzburg	Wuerzburg	Germany	D-97080
26	National Institute of Oncology	Budapest	Hungary	1122
27	Rambam Medical Center	Haifa	Israel	31096
28	Wolfson Medical Center	Holon	Israel	58100