Combination Chemotherapy in Treating Patients With Recurrent or Metastatic Colorectal Cancer

NCT00003287 | Completed Phase 3

• 1 other identifier: EORTC-05963
• Study Type: interventional
• Target: 554
• Locations: 9 countries
• Sites: 36

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.

Conditions

Colorectal Cancer

Keywords

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

Interventions

FOLFOX regimen DRUG

fluorouracil DRUG

leucovorin calcium DRUG

oxaliplatin DRUG

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• European Organisation for Research and Treatment of Cancer - EORTC: lead

Study Sites (36)

Krankenanstalt Rudolfstiftung

Vienna (Wien), A-1030, Austria

Location

VZW Monica Campus Eewnfeestkliniek

Antwerp, 2010, Belgium

Location

Hopital Saint Jean

Brussels, B-1000, Belgium

Location

Cliniques Universitaires Saint-Luc

Brussels (Bruxelles), 1200, Belgium

Location

Centre Hospitalier Notre Dame - Reine Fabiola

Charleroi, 6000, Belgium

Location

Les Cliniques Saint-Joseph ASBL

Liege (Luik), B 4000, Belgium

Location

CHU Sart-Tilman

Liège, B-4000, Belgium

Location

Clinique Sainte Elisabeth

Namur, 5000, Belgium

Location

Centre Hospitalier de Lorraine

Virton, 6762, Belgium

Location

Sunnybrook and Women's College Health Sciences Centre

North York, Ontario, M4N 3M5, Canada

Location

Centre Hospitalier Regional de Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

Centre Hospitalier de la Cote Basque

Bayonne, 64109, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63011, France

Location

Clinique du Parc

Croix, 59170, France

Location

Centre de Lute Contre le Cancer,Georges-Francois Leclerc

Dijon, 21079, France

Location

Hopital Perpetuel Secours

Levallois-Perret, 92300, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Hospital Regional Universitaire de Limoges

Limoges, 87042, France

Location

Hopital Notre-Dame de Bon Secours

Metz, 55038, France

Location

Centre Hospitalier de Montlucon

Montluçon, 03109, France

Location

Clinique Hartmann

Neuilly-sur-Seine, 92200, France

Location

Hopital Cochin

Paris, 75674, France

Location

Centre Rene Huguenin

Saint-Cloud, 92211, France

Location

Hopital Bellevue

Saint-Etienne, 42022, France

Location

Hopital Paul Brousse

Villejuif, 94804, France

Location

Klinikum der Friedrich-Schiller Universitaet Jena

Jena, D-07740, Germany

Location

University Hospital of Heraklion

Iraklion (Heraklion), Crete, 71110, Greece

Location

Universita G.D'Annunzio Di Chieti

Chieti, 66100, Italy

Location

Azienda Ospedale S. Luigi - Universita Di Torino

Orbassano, (Torino), 10043, Italy

Location

Fondazione Salvatore Maugeri

Pavia, I-27100, Italy

Location

Azienda Ospedaliera "Santa Maria Degli Angeli"

Pordenone, 33170, Italy

Location

Ospedale Oncologico Regionale

Rionero in Vulture, I-58028, Italy

Location

Istituti Fisioterapici Ospitalieri - Roma

Rome, 00161, Italy

Location

Haukeland Hospital - University of Bergen

Bergen, N-5021, Norway

Location

Hospital Fernando Fonseca

Amadora, P-2700, Portugal

Location

Hospital De Santo Antonio Dos Capuchos

Lisbon (Lisboa), 1100, Portugal

Location

Related 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, 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.

  PMID: 18421055 BACKGROUND

• 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.

  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.

  PMID: 9291901 BACKGROUND

• 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.

  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.

  PMID: 21859417 RESULT

• 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.

  PMID: 16877722 RESULT

• 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.

  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.

  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.

  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.

  RESULT

MeSH Terms

Conditions

Colorectal Neoplasms; Colonic Neoplasms; Rectal Neoplasms

Interventions

Folfox protocol; Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• Francis Levi, MD, PhD

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

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 1, 1999
• First Posted: January 23, 2004
• Study Start: March 1, 1998
• Primary Completion: March 1, 2002
• Last Updated: July 2, 2012

Record last verified: 2012-06

Locations

PT (2); AU (1); BE (8); CA (2); DE (1); FR (14); GR (1); NO (1); IT (6)