Combination Chemotherapy in Treating Patients With Recurrent or Metastatic Colorectal Cancer

NCT ID: NCT00003287

Last Updated: 2012-07-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 554 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-03-31

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.

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Primary Study Purpose: TREATMENT

Interventions

FOLFOX regimen

Intervention Type: DRUG

fluorouracil

Intervention Type: DRUG

leucovorin calcium

Intervention Type: DRUG

oxaliplatin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Organisation for Research and Treatment of Cancer - EORTC

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Francis Levi, MD, PhD

Role: STUDY_CHAIR

Institut de Cancerologie et D'Immunogenetique at Hopital Paul-Brousse

Locations

Krankenanstalt Rudolfstiftung

Vienna (Wien), , Austria

VZW Monica Campus Eewnfeestkliniek

Antwerp, , Belgium

Hopital Saint Jean

Brussels, , Belgium

Cliniques Universitaires Saint-Luc

Brussels (Bruxelles), , Belgium

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, , Belgium

Les Cliniques Saint-Joseph ASBL

Liege (Luik), , Belgium

CHU Sart-Tilman

Liège, , Belgium

Clinique Sainte Elisabeth

Namur, , Belgium

Centre Hospitalier de Lorraine

Virton, , Belgium

Sunnybrook and Women's College Health Sciences Centre

North York, Ontario, Canada

Centre Hospitalier Regional de Rimouski

Rimouski, Quebec, Canada

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

Montluçon, , 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, , France

Klinikum der Friedrich-Schiller Universitaet Jena

Jena, , Germany

University Hospital of Heraklion

Iraklion (Heraklion), Crete, Greece

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, , Italy

Haukeland Hospital - University of Bergen

Bergen, , Norway

Hospital Fernando Fonseca

Amadora, , Portugal

Hospital De Santo Antonio Dos Capuchos

Lisbon (Lisboa), , Portugal

Countries

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

References

Efficace F, Innominato PF, Bjarnason G, Coens C, Humblet Y, Tumolo S, Genet D, Tampellini M, Bottomley A, Garufi C, Focan C, Giacchetti S, Levi 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.

Reference Type: BACKGROUND

PMID: 18421055 (View on PubMed)

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.

Reference Type: BACKGROUND

Levi 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. doi: 10.1016/s0140-6736(97)03358-8.

Reference Type: BACKGROUND

PMID: 9291901 (View on PubMed)

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.

Reference Type: BACKGROUND

Innominato PF, Giacchetti S, Moreau T, Smaaland R, Focan C, Bjarnason GA, Garufi C, Iacobelli S, Tampellini M, Tumolo S, Carvalho C, Karaboue A, Levi F; ARTBC International Chronotherapy Group. Prediction of survival by neutropenia according to delivery schedule of oxaliplatin-5-Fluorouracil-leucovorin for metastatic colorectal cancer in a randomized international trial (EORTC 05963). Chronobiol Int. 2011 Aug;28(7):586-600. doi: 10.3109/07420528.2011.597532.

Reference Type: RESULT

PMID: 21859417 (View on PubMed)

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, Levi F; European Organisation for Research and Treatment of Cancer Chronotherapy Group. Phase III trial comparing 4-day chronomodulated therapy versus 2-day conventional delivery of fluorouracil, leucovorin, and oxaliplatin as first-line chemotherapy of metastatic colorectal cancer: the European Organisation for Research and Treatment of Cancer Chronotherapy Group. J Clin Oncol. 2006 Aug 1;24(22):3562-9. doi: 10.1200/JCO.2006.06.1440.

Reference Type: RESULT

PMID: 16877722 (View on PubMed)

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, leucovorin and oxaliplatin: a companion study to EORTC 05963. [Abstract] J Clin Oncol 23 (Suppl 16): A-3553, 259s, 2005.

Reference Type: RESULT

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 oxaliplatin : an international multicenter study (EORTC 05963). [Abstract] J Clin Oncol 23 (Suppl 16): A-8029, 736s, 2005.

Reference Type: RESULT

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 Oncol 23 (Suppl 16): A-3587, 267s, 2005.

Reference Type: RESULT

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. [Abstract] Proceedings of the American Society of Clinical Oncology 21: A-2231, 2002.

Reference Type: RESULT

Other Identifiers

EORTC-05963

Identifier Type: -

Identifier Source: secondary_id

EORTC-05963

Identifier Type: -

Identifier Source: org_study_id