Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer - Full Text View

Sponsored by:	European Organization for Research and Treatment of Cancer
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00064181

Purpose

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	Intervention	Phase
Colorectal Cancer	Drug: FOLFIRI regimen Drug: capecitabine Drug: celecoxib Drug: fluorouracil Drug: irinotecan hydrochloride Drug: leucovorin calcium	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Active Control
Official Title:	Irinotecan Combined With Infusional 5-FU/Folinic Acid or Capecitabine and the Role of Celecoxib in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Leucovorin Citrovorum factor Irinotecan U 101440E Irinotecan hydrochloride Capecitabine Celecoxib Leucovorin Calcium Folinic acid calcium salt pentahydrate

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

May 2003

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064181

Locations

Belgium
Academisch Ziekenhuis der Vrije Universiteit Brussel
Brussels, Belgium, 1090
Cazk Groeninghe - Campus St-Niklaas
Kortrijk, Belgium, B-8500
Institut Jules Bordet
Brussels, Belgium, 1000
St. Elizabeth Ziekenhuis
Turnhout, Belgium, 2300
Universitair Ziekenhuis Antwerpen
Edegem, Belgium, B-2650
Ziekenhuis Network Antwerpen Middelheim
Antwerp, Belgium, 2020
Egypt
National Cancer Institute - Cairo
Cairo, Egypt
Germany
Klinikum der Albert - Ludwigs - Universitaet Freiburg
Freiburg, Germany, D-79106
Allgemeines Krankenhaus Hagen
Hagen, Germany, D-58095
Charite - Campus Charite Mitte
Berlin, Germany, D-10117
Eberhard Karls Universitaet
Tuebingen, Germany, D-72076
General Hospital
Celle, Germany, 29223
Kliniken Essen - Mitte
Essen, Germany, D-45136
Allgemeines Krankenhaus Altona
Hamburg, Germany, 22763
Klinikum der J.W. Goethe Universitaet
Frankfurt, Germany, D-60590
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
Munich, Germany, D-81675
Kreiskrankenhaus Meissen
Meissen, Germany, D-01662
Onkologische Schwerpunktpraxis Leer
Leer, Germany, D-26789
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
Magdeburg, Germany, D-39120
Universitaets-Hautklinik Wuerzburg
Wuerzburg, Germany, D-97080
St. Marien Hospital
Hamm, Germany, 59065
Universitaets-Krankenhaus Eppendorf
Hamburg, Germany, D-20246
Universitatsklinikum Carl Gustav Carl Carus
Dresden, Germany, D-01307
Vinzentiuskrankenhaus
Landau, Germany, D-76829
Westpfalz-Klinikum GmbH
Kaiserslautern, Germany, D-67653
Hungary
National Institute of Oncology
Budapest, Hungary, 1122
Israel
Rambam Medical Center
Haifa, Israel, 31096
Wolfson Medical Center
Holon, Israel, 58100

Sponsors and Collaborators

European Organization for Research and Treatment of Cancer

Investigators

Investigator:

Claus-Henning Koehne, MD

Klinikum Oldenburg

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

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 with infusional 5-fluorouracil/folinic acid or capecitabine plus celecoxib or placebo in the first-line treatment of patients with metastatic colorectal cancer. EORTC study 40015. Ann Oncol. 2007 Dec 6; [Epub ahead of print]

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. [Abstract] J Clin Oncol 24 (Suppl 18): A-3577, 2006.

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 Clin Oncol 23 (Suppl 16): A-3525, 252s, 2005.

Study ID Numbers:	CDR0000309572, EORTC-40015
Study First Received:	July 8, 2003
Last Updated:	January 3, 2009
ClinicalTrials.gov Identifier:	NCT00064181 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adenocarcinoma of the colon
adenocarcinoma of the rectum
stage IV colon cancer
stage IV rectal cancer

Study placed in the following topic categories:

Anti-Inflammatory Agents
Antimetabolites
Immunologic Factors
Gastrointestinal Diseases
Rectal Neoplasms
Colonic Diseases
Irinotecan
Folate
Leucovorin
Rectal Diseases
Vitamin B9
Vitamins
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Micronutrients

Capecitabine
Vitamin B Complex
Digestive System Neoplasms
Celecoxib
Cyclooxygenase Inhibitors
Rectal Neoplasm
Trace Elements
Folinic Acid
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Camptothecin
Folic Acid
Calcium, Dietary
Rectal Cancer

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Gastrointestinal Diseases
Antineoplastic Agents
Physiological Effects of Drugs
Colonic Diseases
Irinotecan
Leucovorin
Rectal Diseases
Neoplasms by Site
Sensory System Agents
Vitamins

Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Micronutrients
Capecitabine
Vitamin B Complex
Digestive System Neoplasms
Celecoxib
Growth Substances
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Intestinal Diseases
Immunosuppressive Agents
Intestinal Neoplasms
Camptothecin

ClinicalTrials.gov processed this record on July 02, 2009