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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00064181
• Other study ID #: EORTC-40015
• Secondary ID: EORTC-40015
• Status: Completed
• Phase: Phase 3
• First received: July 8, 2003
• Last updated: September 20, 2012
• Start date: May 2003

Study information

• Verified date: September 2012
• Source: European Organisation for Research and Treatment of Cancer - EORTC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. primary completion date: January 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• FOLFIRI regimen

• capecitabine

• celecoxib

• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

Locations

Country	Name	City	State
Belgium	Ziekenhuis Network Antwerpen Middelheim	Antwerp
Belgium	Academisch Ziekenhuis der Vrije Universiteit Brussel	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Cazk Groeninghe - Campus St-Niklaas	Kortrijk
Belgium	St. Elizabeth Ziekenhuis	Turnhout
Egypt	National Cancer Institute - Cairo	Cairo
Germany	Charite - Campus Charite Mitte	Berlin
Germany	General Hospital	Celle
Germany	Universitatsklinikum Carl Gustav Carl Carus	Dresden
Germany	Kliniken Essen - Mitte	Essen
Germany	Klinikum der J.W. Goethe Universitaet	Frankfurt
Germany	Klinikum der Albert - Ludwigs - Universitaet Freiburg	Freiburg
Germany	Allgemeines Krankenhaus Hagen	Hagen
Germany	Allgemeines Krankenhaus Altona	Hamburg
Germany	Universitaets-Krankenhaus Eppendorf	Hamburg
Germany	St. Marien Hospital	Hamm
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Vinzentiuskrankenhaus	Landau
Germany	Onkologische Schwerpunktpraxis Leer	Leer
Germany	Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg	Magdeburg
Germany	Kreiskrankenhaus Meissen	Meissen
Germany	Klinikum Rechts Der Isar - Technische Universitaet Muenchen	Munich
Germany	Eberhard Karls Universitaet	Tuebingen
Germany	Universitaets-Hautklinik Wuerzburg	Wuerzburg
Hungary	National Institute of Oncology	Budapest
Israel	Rambam Medical Center	Haifa
Israel	Wolfson Medical Center	Holon

Sponsors (1)

Lead Sponsor	Collaborator
European Organisation for Research and Treatment of Cancer - EORTC

Countries where clinical trial is conducted

Belgium,  Egypt,  Germany,  Hungary,  Israel, 

References & Publications (3)

De Grève J, Koehne C, Hartmann J, et al.: Capecitabine plus irinotecan versus 5-FU/FA/irinotecan ± celecoxib in first line treatment of metastatic colorectal cancer (CRC). Long-term results of the prospective multicenter EORTC phase III study 40015. [Abst

Kohne C, De Greve J, Bokemeyer C, et al.: Capecitabine plus irinotecan versus 5-FU/FA/irinotecan +/- celecoxib in first line treatment of metastatic colorectal cancer. Safety results of the prospective multicenter EORTC phase III study 40015. [Abstract] J

Köhne CH, De Greve J, Hartmann JT, Lang I, Vergauwe P, Becker K, Braumann D, Joosens E, Müller L, Janssens J, Bokemeyer C, Reimer P, Link H, Späth-Schwalbe E, Wilke HJ, Bleiberg H, Van Den Brande J, Debois M, Bethe U, Van Cutsem E. Irinotecan combined wit — View Citation