Back to resultsCombination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer
Primary Purpose
Colorectal Cancer
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
FOLFIRI regimen
capecitabine
celecoxib
fluorouracil
irinotecan hydrochloride
leucovorin calcium
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Cancer focused on measuring adenocarcinoma of the colon, adenocarcinoma of the rectum, stage IV colon cancer, stage IV rectal cancer
Eligibility 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
Sites / Locations
- Ziekenhuis Network Antwerpen Middelheim
- Institut Jules Bordet
- Academisch Ziekenhuis der Vrije Universiteit Brussel
- Universitair Ziekenhuis Antwerpen
- Cazk Groeninghe - Campus St-Niklaas
- St. Elizabeth Ziekenhuis
- National Cancer Institute - Cairo
- Charite - Campus Charite Mitte
- General Hospital
- Universitatsklinikum Carl Gustav Carl Carus
- Kliniken Essen - Mitte
- Klinikum der J.W. Goethe Universitaet
- Klinikum der Albert - Ludwigs - Universitaet Freiburg
- Allgemeines Krankenhaus Hagen
- Allgemeines Krankenhaus Altona
- Universitaets-Krankenhaus Eppendorf
- St. Marien Hospital
- Westpfalz-Klinikum GmbH
- Vinzentiuskrankenhaus
- Onkologische Schwerpunktpraxis Leer
- Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
- Kreiskrankenhaus Meissen
- Klinikum Rechts Der Isar - Technische Universitaet Muenchen
- Eberhard Karls Universitaet
- Universitaets-Hautklinik Wuerzburg
- National Institute of Oncology
- Rambam Medical Center
- Wolfson Medical Center
Outcomes
Primary Outcome Measures
Secondary Outcome Measures
Full Information
NCT ID
NCT00064181
First Posted
July 8, 2003
Last Updated
September 20, 2012
Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
1. Study Identification
Unique Protocol Identification Number
NCT00064181
Brief Title
Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer
Official Title
Irinotecan Combined With Infusional 5-FU/Folinic Acid or Capecitabine and the Role of Celecoxib in Patients With Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2012
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
January 2005 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
European Organisation for Research and Treatment of Cancer - EORTC
4. Oversight
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Cancer
Keywords
adenocarcinoma of the colon, adenocarcinoma of the rectum, stage IV colon cancer, stage IV rectal cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Masking
Double
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
FOLFIRI regimen
Intervention Type
Drug
Intervention Name(s)
capecitabine
Intervention Type
Drug
Intervention Name(s)
celecoxib
Intervention Type
Drug
Intervention Name(s)
fluorouracil
Intervention Type
Drug
Intervention Name(s)
irinotecan hydrochloride
Intervention Type
Drug
Intervention Name(s)
leucovorin calcium
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claus-Henning Koehne, MD
Organizational Affiliation
Klinikum Oldenburg
Official's Role
Study Chair
Facility Information:
Facility Name
Ziekenhuis Network Antwerpen Middelheim
City
Antwerp
ZIP/Postal Code
2020
Country
Belgium
Facility Name
Institut Jules Bordet
City
Brussels
ZIP/Postal Code
1000
Country
Belgium
Facility Name
Academisch Ziekenhuis der Vrije Universiteit Brussel
City
Brussels
ZIP/Postal Code
1090
Country
Belgium
Facility Name
Universitair Ziekenhuis Antwerpen
City
Edegem
ZIP/Postal Code
B-2650
Country
Belgium
Facility Name
Cazk Groeninghe - Campus St-Niklaas
City
Kortrijk
ZIP/Postal Code
B-8500
Country
Belgium
Facility Name
St. Elizabeth Ziekenhuis
City
Turnhout
ZIP/Postal Code
2300
Country
Belgium
Facility Name
National Cancer Institute - Cairo
City
Cairo
Country
Egypt
Facility Name
Charite - Campus Charite Mitte
City
Berlin
ZIP/Postal Code
D-10117
Country
Germany
Facility Name
General Hospital
City
Celle
ZIP/Postal Code
29223
Country
Germany
Facility Name
Universitatsklinikum Carl Gustav Carl Carus
City
Dresden
ZIP/Postal Code
D-01307
Country
Germany
Facility Name
Kliniken Essen - Mitte
City
Essen
ZIP/Postal Code
D-45136
Country
Germany
Facility Name
Klinikum der J.W. Goethe Universitaet
City
Frankfurt
ZIP/Postal Code
D-60590
Country
Germany
Facility Name
Klinikum der Albert - Ludwigs - Universitaet Freiburg
City
Freiburg
ZIP/Postal Code
D-79106
Country
Germany
Facility Name
Allgemeines Krankenhaus Hagen
City
Hagen
ZIP/Postal Code
D-58095
Country
Germany
Facility Name
Allgemeines Krankenhaus Altona
City
Hamburg
ZIP/Postal Code
22763
Country
Germany
Facility Name
Universitaets-Krankenhaus Eppendorf
City
Hamburg
ZIP/Postal Code
D-20246
Country
Germany
Facility Name
St. Marien Hospital
City
Hamm
ZIP/Postal Code
59065
Country
Germany
Facility Name
Westpfalz-Klinikum GmbH
City
Kaiserslautern
ZIP/Postal Code
D-67653
Country
Germany
Facility Name
Vinzentiuskrankenhaus
City
Landau
ZIP/Postal Code
D-76829
Country
Germany
Facility Name
Onkologische Schwerpunktpraxis Leer
City
Leer
ZIP/Postal Code
D-26789
Country
Germany
Facility Name
Universitaetsklinkum Magdeburg der Otto-von-Guericke-Universitaet Magdeburg
City
Magdeburg
ZIP/Postal Code
D-39120
Country
Germany
Facility Name
Kreiskrankenhaus Meissen
City
Meissen
ZIP/Postal Code
D-01662
Country
Germany
Facility Name
Klinikum Rechts Der Isar - Technische Universitaet Muenchen
City
Munich
ZIP/Postal Code
D-81675
Country
Germany
Facility Name
Eberhard Karls Universitaet
City
Tuebingen
ZIP/Postal Code
D-72076
Country
Germany
Facility Name
Universitaets-Hautklinik Wuerzburg
City
Wuerzburg
ZIP/Postal Code
D-97080
Country
Germany
Facility Name
National Institute of Oncology
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Rambam Medical Center
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
Wolfson Medical Center
City
Holon
ZIP/Postal Code
58100
Country
Israel
12. IPD Sharing Statement
Citations:
PubMed Identifier
18065406
Citation
Kohne CH, De Greve J, Hartmann JT, Lang I, Vergauwe P, Becker K, Braumann D, Joosens E, Muller L, Janssens J, Bokemeyer C, Reimer P, Link H, Spath-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. 2008 May;19(5):920-6. doi: 10.1093/annonc/mdm544. Epub 2007 Dec 6.
Results Reference
result
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Learn more about this trial
Combination Chemotherapy With or Without Celecoxib in Treating Patients With Metastatic Colorectal Cancer
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