Combination Chemotherapy in Treating Patients With Recurrent or Metastatic Colorectal Cancer

Sponsor

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

Overall Status

Completed

CT.gov ID

NCT00003287

Collaborator

(none)

554

Enrollment

Locations

15.4

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of combination chemotherapy is more effective in treating patients with recurrent or metastatic colorectal cancer.

PURPOSE: Randomized phase III trial to study the effectiveness of combining fluorouracil, leucovorin, and oxaliplatin in different ways in treating patients with recurrent or metastatic colorectal cancer.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Cancer	Drug: FOLFOX regimen Drug: fluorouracil Drug: leucovorin calcium Drug: oxaliplatin	Phase 3

Detailed Description

OBJECTIVES: I. Compare the effects of chronomodulated versus nonchronomodulated infusional administration of a 3 drug high-dose chemotherapy regimen on survival in patients with locoregionally recurrent or metastatic colorectal cancer. II. Assess the antitumor effect of the combination of fluorouracil, leucovorin calcium, and oxaliplatin given as first line chemotherapy in these patients. III. Assess the response rate and toxicity of this treatment in these patients. IV. Assess the quality of life of patients receiving this treatment.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to performance status (ECOG 0-1 vs 2), extent of liver involvement (none vs less than 25% vs 25% or greater), and institution. Patients are randomized into 2 arms: Arm I (chronotherapy): Patients receive a 4 day infusion of fluorouracil, leucovorin calcium, and oxaliplatin administered via pump using chronomodulated delivery rates. Arm II (fixed infusion rate): Patients receive leucovorin calcium and oxaliplatin as 2 hour concurrent infusions followed by fluorouracil as a 22 hour infusion on day 1. On day 2, patients receive a 2 hour infusion of leucovorin calcium followed by a 22 hour infusion of fluorouracil. For patients on both arms, courses repeat every 2 weeks until the occurrence of disease progression, severe toxicity, or complete remission for a minimum of 4 months. Quality of life is assessed prior to treatment and 2 weeks after courses 4 and 8. Patients are followed for survival.

PROJECTED ACCRUAL: A total of 554 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

554 participants

Allocation:

Randomized

Primary Purpose:

Treatment

Official Title:

First Line Infusional 5-Fluorouracil, Folinic Acid and Oxaliplatin for Metastatic Colorectal Cancer or Loco-Regional Recurrency - Role of Chronomodulated Delivery Upon Survival - A Multicenter Randomized Phase III Trial

Study Start Date :

Mar 1, 1998

Actual Primary Completion Date :

Mar 1, 2002

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS: Histologically proven locoregionally recurrent or metastatic adenocarcinoma of the colon or rectum Histologic or cytologic proof of adenocarcinoma consistent with colorectal cancer in a solitary lesion if plasma carcinoembryonic antigen level is no greater than normal Metastases not limited to bone, pleural effusion, or ascites Surgically resectable metastases not eligible No symptomatic brain metastasis At least one bidimensionally measurable lesion measuring at least 20 mm in one diameter outside a previously irradiated area

PATIENT CHARACTERISTICS: Age: 18 to 75 Performance status: ECOG 0-2 Life expectancy: Not specified Hematopoietic: Absolute neutrophil count at least 2,000/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin no greater than 3 times upper limit of normal Renal: No uncontrolled hypercalcemia Cardiovascular: No significant cardiac disease Pulmonary: No severe respiratory illness Neurologic: No peripheral sensory neuropathy Other: No uncontrolled infection or chronic disease No second malignancy except basal cell carcinoma of the skin or in situ carcinoma of the cervix

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior immunotherapy for locoregionally recurrent or metastatic colorectal cancer No concurrent prophylactic growth factor Chemotherapy: No prior chemotherapy for locoregionally recurrent or metastatic colorectal cancer At least 6 months since adjuvant chemotherapy Endocrine therapy: No prior hormone therapy for locoregionally recurrent or metastatic colorectal cancer No concurrent corticosteroids Radiotherapy: See Disease Characteristics No prior radiotherapy for locoregionally recurrent or metastatic colorectal cancer Concurrent localized analgesic radiotherapy of a bone lesion permitted unless indicative of disease progression Surgery: No prior surgery for locoregionally recurrent or metastatic colorectal cancer Other: No other concurrent investigational drug

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Krankenanstalt Rudolfstiftung	Vienna (Wien)		Austria	A-1030
2	VZW Monica Campus Eewnfeestkliniek	Antwerpen		Belgium	2010
3	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)		Belgium	1200
4	Hopital Saint Jean	Brussels		Belgium	B-1000
5	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi		Belgium	6000
6	Les Cliniques Saint-Joseph ASBL	Liege (Luik)		Belgium	B 4000
7	CHU Sart-Tilman	Liege		Belgium	B-4000
8	Clinique Sainte Elisabeth	Namur		Belgium	5000
9	Centre Hospitalier de Lorraine	Virton		Belgium	6762
10	Sunnybrook and Women's College Health Sciences Centre	North York	Ontario	Canada	M4N 3M5
11	Centre Hospitalier Regional de Rimouski	Rimouski	Quebec	Canada	G5L 5T1
12	Centre Hospitalier de la Cote Basque	Bayonne		France	64109
13	Centre Jean Perrin	Clermont-Ferrand		France	63011
14	Clinique du Parc	Croix		France	59170
15	Centre de Lute Contre le Cancer,Georges-Francois Leclerc	Dijon		France	21079
16	Hopital Perpetuel Secours	Levallois-Perret		France	92300
17	Centre Oscar Lambret	Lille		France	59020
18	Centre Hospital Regional Universitaire de Limoges	Limoges		France	87042
19	Hopital Notre-Dame de Bon Secours	Metz		France	55038
20	Centre Hospitalier de Montlucon	Montlucon		France	03109
21	Clinique Hartmann	Neuilly sur Seine		France	92200
22	Hopital Cochin	Paris		France	75674
23	Centre Rene Huguenin	Saint Cloud		France	92211
24	Hopital Bellevue	Saint Etienne		France	42022
25	Hopital Paul Brousse	Villejuif		France	94804
26	Klinikum der Friedrich-Schiller Universitaet Jena	Jena		Germany	D-07740
27	University Hospital of Heraklion	Iraklion (Heraklion)	Crete	Greece	71110
28	Universita G.D'Annunzio Di Chieti	Chieti		Italy	66100
29	Azienda Ospedale S. Luigi - Universita Di Torino	Orbassano, (Torino)		Italy	10043
30	Fondazione Salvatore Maugeri	Pavia		Italy	I-27100
31	Azienda Ospedaliera "Santa Maria Degli Angeli"	Pordenone		Italy	33170
32	Ospedale Oncologico Regionale	RIONERO in VULTURE		Italy	I-58028
33	Istituti Fisioterapici Ospitalieri - Roma	Rome		Italy	00161
34	Haukeland Hospital - University of Bergen	Bergen		Norway	N-5021
35	Hospital Fernando Fonseca	Amadora		Portugal	P-2700
36	Hospital De Santo Antonio Dos Capuchos	Lisbon (Lisboa)		Portugal	1100