Combination Chemotherapy as First-Line Therapy in Treating Older Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery

Colorectal Cancer Clinical Trial

Official title:

Randomized Study of Classic vs Simplified Leucovorin Calcium and Fluorouracil With or Without Irinotecan in Patients Aged At Least 75 Years With Advanced Colorectal Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00303771
• Other study ID #: CDR0000453855
• Secondary ID: FFCD-2001-02EU-2
• Status: Completed
• Phase: Phase 3
• First received: March 15, 2006
• Last updated: May 27, 2016
• Start date: June 2003
• Est. completion date: January 2011

Study information

• Verified date: May 2016
• Source: Federation Francophone de Cancerologie Digestive
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as fluorouracil, leucovorin, and irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) in different doses or combinations may kill more tumor cells. It is not yet known which combination chemotherapy regimen is more effective in treating colorectal cancer.

PURPOSE: This randomized clinical trial is studying how well fluorouracil works together with leucovorin with or without irinotecan in treating older patients with metastatic colorectal cancer .

Description:

OBJECTIVES:

Primary

• Compare the progression-free survival of elderly patients with unresectable metastatic colorectal cancer treated with 1 of 2 different chemotherapy regimens comprising fluorouracil and leucovorin calcium with vs without irinotecan hydrochloride.

Secondary

• Compare the tumor response rate and overall survival of patients treated with these regimens.

• Compare the tolerability of these regimens in these patients.

• Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, multicenter, prospective study. Patients are stratified according to participating center, gender, Karnofsky score (60-70% vs 80-90% vs 100%), associated comorbidities (Charlson Index 0 vs 1-2 vs 3+), age (75 to 79 years vs ≥ 80 years), alkaline phosphatase level (≤ 2 times normal vs > 2 times normal), and prior adjuvant chemotherapy (yes vs no). Patients are randomized to 1 of 4 treatment arms.

• Arm I: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 22 hours on days 1 and 2.

• Arm II: Patients receive leucovorin calcium IV over 2 hours and fluorouracil IV continuously over 46 hours on days 1 and 2.

• Arm III: Patients receive leucovorin calcium and fluorouracil as in arm I and irinotecan hydrochloride IV over 90 minutes on day 1.

• Arm IV: Patients receive leucovorin calcium and fluorouracil as in arm II and irinotecan hydrochloride as in arm III.

In all arms, treatment repeats every 14 days in the absence of disease progression or unacceptable toxicity.

Patients undergo surgery within 3-10 weeks after completing chemotherapy.

Quality of life is assessed at baseline and then every 2 months thereafter.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 282 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 282
• Est. completion date: January 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 75 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed adenocarcinoma of the colon or rectum

• Metastatic disease

• Unresectable disease

• Measurable disease that is outside the field of prior irradiation

• No brain metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Transaminases = 5 times normal

• Bilirubin = 1.5 times normal

• Alkaline phosphatase < 3 times normal (5 times normal if due to hepatic involvement)

• Creatinine clearance > 45 mL/min

• Life expectancy > 3 months

• No psychological, social, or geographical situation that would preclude study treatment

• No chronic diarrhea or enteropathy

• No coronary insufficiency or symptomatic cardiac disease

• No other malignancy unless curatively treated

• No contraindication to chemotherapy

PRIOR CONCURRENT THERAPY:

• At least 6 months since prior adjuvant chemotherapy for the primary tumor

• No prior extensive resection

• No other concurrent anticancer therapy

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• fluorouracil

• irinotecan hydrochloride

• leucovorin calcium

Locations

Country	Name	City	State
France	Centre Hospitalier d'Abbeville	Abbeville
France	Centre Hospitalier D'Agen	Agen
France	Centre hospitalier d'Alencon	Alencon
France	Clinique De Rochebelle	Ales
France	Centre Hospitalier Universitaire d'Amiens	Amiens
France	Centre Hospitalier d'Annecy	Annecy
France	Hopital Duffaut	Avignon
France	Institut Sainte Catherine	Avignon
France	Centre Hospitalier de Blois	Blois
France	Hopital Saint Andre	Bordeaux
France	Centre Hospitalier Docteur Duchenne	Boulogne Sur Mer
France	Hopital Ambroise Pare	Boulogne-Billancourt
France	C.H. Bourg En Bresse	Bourg En Bresse
France	Centre Hospitalier Pierre Oudot	Bourgoin-Jallieu
France	Centre Hospitalier de Briey	Briey
France	Centre Medical de Bligny	Briis-Sous-Forges
France	Centre Hospitalier de Chalons-en-Champagne	Chalons-en-Champagne
France	Centre hospitalier de Charleville Mezieres	Charleville-Mezieres cedex
France	Centre Hospitalier de Chateaubriant	Chateaubriant cedex
France	Hopital Louis Pasteur	Colmar
France	Louis Mourier Hospital	Colombes Cedex
France	Centre Hospitalier Universitaire Henri Mondor	Creteil
France	Centre Hospitalier de Digne les Bains	Digne Cedex
France	Hopital Du Bocage	Dijon
France	Centre Hospitalier de Dreux	Dreux
France	Centre Hospitalier Intercommunal St. Aubin les Elbeuf	Elbeuf
France	Clinique Saint Vincent	Epernay
France	CHU de Grenoble - Hopital Michallon	Grenoble
France	Clinique Pasteur	Guilherand Granges
France	Centre Hospitalier de Haguenau	Haguenau
France	Centre Hospitalier Departemental	La Roche Sur Yon
France	Centre Hospitalier Universitaire de Bicetre	Le Kremlin Bicetre
France	Hopital Perpetuel Secours	Levallois
France	Hopital Robert Boulin	Libourne
France	Centre Hospital Universitaire Hop Huriez	Lille
France	Centre Hospital Regional Universitaire de Limoges	Limoges
France	Centre Hospitalier General	Longjumeau
France	Clinique Saint Jean	Lyon
France	Hopital Edouard Herriot - Lyon	Lyon
France	CHU de la Timone	Marseille
France	CHU Nord	Marseille
France	Centre Hospitalier de Martigues	Martigues
France	Centre Gray	Maubeuge
France	Centre Hospitalier de Meaux	Meaux
France	Centre Hospitalier General de Mont de Marsan	Mont-de-Marsan
France	Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle	Montpellier
France	CHU de Nancy - Hopitaux de Brabois	Nancy
France	Centre Hospitalier de Nevers	Nevers
France	Hopital de l'Archet CHU de Nice	Nice
France	C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau	Nimes
France	Centre Hospitalier d'Orange	Orange
France	CHU Pitie-Salpetriere	Paris
France	Hopital Bichat - Claude Bernard	Paris
France	Hopital Cochin	Paris
France	Hopital d'Instruction des Armees du Val de Grace	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	Hopital Tenon	Paris
France	Centre Hospitalier - Pau	Pau
France	Centre Hospitalier de Perpignan	Perpignan
France	Hopital Haut Leveque	Pessac
France	Hopital Rene Dubos	Pontoise
France	CHU - Robert Debre	Reims
France	Polyclinique De Courlancy	Reims
France	Centre Eugene Marquis	Rennes
France	Centre Hospitalier Universitaire de Rouen	Rouen
France	Pole Sante Sarthe et Loir Hopital Pierre Daguet	Sable Sur Sarthe
France	Centre Rene Huguenin	Saint Cloud
France	Hopital d'Instruction des Armees Begin	Saint-Mande
France	Centre Hospitalier de Saint-Quentin	Saint-Quentin
France	Center Hospitalier de Sens	Sens
France	Hopital Foch	Suresnes
France	Centre Hospitalier Valence	Valence
France	Nouvelle Clinique Generale	Valence
France	Centre Hospitalier de Valenciennes	Valenciennes
France	Centre Hospitalier Intercommunal de la Haute-Saone	Vesoul
France	Institut Gustave Roussy	Villejuif
France	Centre Hospitalier de Vire	Vire

Sponsors (1)

Lead Sponsor	Collaborator
Federation Francophone de Cancerologie Digestive

Country where clinical trial is conducted

France, 

References & Publications (4)

Aparicio T, Jouve J, Teillet L, et al.: Geriatric factors to predict toxicity and dose-intensity reduction in FFCD 2001-02 phase III study comparing a first-line chemotherapy of LV5FU2 or FOLFIRI in treatment of metastatic colorectal cancer (mCRC) in elde

Aparicio T, Jouve JL, Teillet L, Gargot D, Subtil F, Le Brun-Ly V, Cretin J, Locher C, Bouché O, Breysacher G, Charneau J, Seitz JF, Gasmi M, Stefani L, Ramdani M, Lecomte T, Mitry E. Geriatric factors predict chemotherapy feasibility: ancillary results o — View Citation

Aparicio T, Lavau-Denes S, Phelip JM, Maillard E, Jouve JL, Gargot D, Gasmi M, Locher C, Adhoute X, Michel P, Khemissa F, Lecomte T, Provençal J, Breysacher G, Legoux JL, Lepère C, Charneau J, Cretin J, Chone L, Azzedine A, Bouché O, Sobhani I, Bedenne L, — View Citation

Mitry E, Phelip JM, Bonnetain F, et al.: Phase III trial of chemotherapy with or without irinotecan in the front-line treatment of metastatic colorectal cancer in elderly patients (FFCD 2001-02 trial): results of a planned interim analysis. [Abstract] Ame

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (survie sans progression)	survie sans progression	2011	No
Secondary	Overall Survival (survie globale)	survie globale	2011	No