Combination Chemotherapy in Treating Patients With Recurrent or Metastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003287
• Other study ID #: EORTC-05963
• Secondary ID: EORTC-05963
• Status: Completed
• Phase: Phase 3
• First received: November 1, 1999
• Last updated: June 29, 2012
• Start date: March 1998

Study information

• Verified date: June 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 554
• Est. primary completion date: March 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• FOLFOX regimen

• fluorouracil

• leucovorin calcium

• oxaliplatin

Locations

Country	Name	City	State
Austria	Krankenanstalt Rudolfstiftung	Vienna (Wien)
Belgium	VZW Monica Campus Eewnfeestkliniek	Antwerpen
Belgium	Hopital Saint Jean	Brussels
Belgium	Cliniques Universitaires Saint-Luc	Brussels (Bruxelles)
Belgium	Centre Hospitalier Notre Dame - Reine Fabiola	Charleroi
Belgium	CHU Sart-Tilman	Liege
Belgium	Les Cliniques Saint-Joseph ASBL	Liege (Luik)
Belgium	Clinique Sainte Elisabeth	Namur
Belgium	Centre Hospitalier de Lorraine	Virton
Canada	Sunnybrook and Women's College Health Sciences Centre	North York	Ontario
Canada	Centre Hospitalier Regional de Rimouski	Rimouski	Quebec
France	Centre Hospitalier de la Cote Basque	Bayonne
France	Centre Jean Perrin	Clermont-Ferrand
France	Clinique du Parc	Croix
France	Centre de Lute Contre le Cancer,Georges-Francois Leclerc	Dijon
France	Hopital Perpetuel Secours	Levallois-Perret
France	Centre Oscar Lambret	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Hopital Notre-Dame de Bon Secours	Metz
France	Centre Hospitalier de Montlucon	Montlucon
France	Clinique Hartmann	Neuilly sur Seine
France	Hopital Cochin	Paris
France	Centre Rene Huguenin	Saint Cloud
France	Hopital Bellevue	Saint Etienne
France	Hopital Paul Brousse	Villejuif
Germany	Klinikum der Friedrich-Schiller Universitaet Jena	Jena
Greece	University Hospital of Heraklion	Iraklion (Heraklion)	Crete
Italy	Universita G.D'Annunzio Di Chieti	Chieti
Italy	Azienda Ospedale S. Luigi - Universita Di Torino	Orbassano, (Torino)
Italy	Fondazione Salvatore Maugeri	Pavia
Italy	Azienda Ospedaliera "Santa Maria Degli Angeli"	Pordenone
Italy	Ospedale Oncologico Regionale	RIONERO in VULTURE
Italy	Istituti Fisioterapici Ospitalieri - Roma	Rome
Norway	Haukeland Hospital - University of Bergen	Bergen
Portugal	Hospital Fernando Fonseca	Amadora
Portugal	Hospital De Santo Antonio Dos Capuchos	Lisbon (Lisboa)

Sponsors (1)

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

Countries where clinical trial is conducted

Austria,  Belgium,  Canada,  France,  Germany,  Greece,  Italy,  Norway,  Portugal, 

References & Publications (10)

Efficace F, Innominato PF, Bjarnason G, Coens C, Humblet Y, Tumolo S, Genet D, Tampellini M, Bottomley A, Garufi C, Focan C, Giacchetti S, Lévi F; Chronotherapy Group of the European Organisation for Research and Treatment of Cancer. Validation of patient's self-reported social functioning as an independent prognostic factor for survival in metastatic colorectal cancer patients: results of an international study by the Chronotherapy Group of the European Organisation for Research and Treatment of Cancer. J Clin Oncol. 2008 Apr 20;26(12):2020-6. doi: 10.1200/JCO.2007.12.3117. — View Citation

Garufi C, Bjarnason GA, Giacchetti S, et al.: Independent prognostic value of the rest/activity circadian rhythm on overall survival (OS) in patients (pts) with metastatic colorectal cancer (MCC) receiving first line chemotherapy with 5-fluorouracil, leuc

Giacchetti S, Bjarnason G, Garufi C, Genet D, Iacobelli S, Tampellini M, Smaaland R, Focan C, Coudert B, Humblet Y, Canon JL, Adenis A, Lo Re G, Carvalho C, Schueller J, Anciaux N, Lentz MA, Baron B, Gorlia T, Lévi F; European Organisation for Research an — View Citation

Giacchetti S, Bjarnason GA, Garufi C, et al.: First line infusion of 5-fluorouracil, leucovorin, oxaliplatin for metastatic colorectal cancer chronomodulated versus conventional delivery. A multicenter randomized trial of the EORTC chronotherapy group. [A

Giacchetti S, Zidani R, Perpoint B, et al.: Phase III trial of 5-fluorouracil (5-FU), folinic acid (FA), with or without oxaliplatin (OXA) in previously untreated patients (pts) with metastatic colorectal cancer (MCC). [Abstract] Proceedings of the American Society of Clinical Oncology 16: A805, 229a, 1997.

Innominato PF, Focan C, Bjarnason GA, et al.: Quality of life (QoL) correlates with the rest/activity circadian rhythm (RAR) in patients (pts) with metastatic colorectal cancer (MCC) on first line chemotherapy with 5-fluorouracil, leucovorin and oxaliplat

Innominato PF, Giacchetti S, Moreau T, Smaaland R, Focan C, Bjarnason GA, Garufi C, Iacobelli S, Tampellini M, Tumolo S, Carvalho C, Karaboué A, Lévi F; ARTBC International Chronotherapy Group. Prediction of survival by neutropenia according to delivery s — View Citation

Lévi F, Gorlia T, Tubiana N, et al.: Gender as a predictor for optimal dynamic scheduling of oxaliplatin, 5-fluorouracil and leucovorin in patients with metastatic colorectal cancer. Results from EORTC randomized phase III trial 05963. [Abstract] J Clin O

Lévi F, Zidani R, Misset JL. Randomised multicentre trial of chronotherapy with oxaliplatin, fluorouracil, and folinic acid in metastatic colorectal cancer. International Organization for Cancer Chronotherapy. Lancet. 1997 Sep 6;350(9079):681-6. — View Citation

Mormont MC, Bleuzen P, Lellouch J, et al.: Prognostic value of circadian rhythm assessment for survival of patients with metastatic colorectal cancer. [Abstract] Proceedings of the American Society of Clinical Oncology 16: A-956, 269a, 1997.