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

NCT ID: NCT00303771

Last Updated: 2016-05-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

282 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-06-30

Study Completion Date

2011-01-31

Brief Summary

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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 .

Detailed Description

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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.

Conditions

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Colorectal Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LV5FU2 classique

LV5FU2 classique

Group Type ACTIVE_COMPARATOR

fluorouracil

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

LV5FU2 classique + irinotécan

LV5FU2 classique + irinotécan

Group Type EXPERIMENTAL

fluorouracil

Intervention Type DRUG

irinotecan hydrochloride

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

LV5FU2 simplifié

LV5FU2 simplifié

Group Type ACTIVE_COMPARATOR

fluorouracil

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

LV5FU2 simplifié+ irinotécan

LV5FU2 simplifié + irinotécan

Group Type EXPERIMENTAL

fluorouracil

Intervention Type DRUG

irinotecan hydrochloride

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

Interventions

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fluorouracil

Intervention Type DRUG

irinotecan hydrochloride

Intervention Type DRUG

leucovorin calcium

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

75 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Federation Francophone de Cancerologie Digestive

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emmanuel Mitry, MD, PhD

Role: STUDY_CHAIR

Hopital Ambroise Pare

Locations

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Centre Hospitalier d'Abbeville

Abbeville, , France

Site Status

Centre Hospitalier D'Agen

Agen, , France

Site Status

Centre hospitalier d'Alencon

Alençon, , France

Site Status

Clinique De Rochebelle

Alès, , France

Site Status

Centre Hospitalier Universitaire d'Amiens

Amiens, , France

Site Status

Centre Hospitalier d'Annecy

Annecy, , France

Site Status

Institut Sainte Catherine

Avignon, , France

Site Status

Hopital Duffaut

Avignon, , France

Site Status

Centre Hospitalier de Blois

Blois, , France

Site Status

Hopital Saint Andre

Bordeaux, , France

Site Status

Hopital Ambroise Pare

Boulogne-Billancourt, , France

Site Status

Centre Hospitalier Docteur Duchenne

Boulogne-sur-Mer, , France

Site Status

C.H. Bourg En Bresse

Bourg-en-Bresse, , France

Site Status

Centre Hospitalier Pierre Oudot

Bourgoin, , France

Site Status

Centre Hospitalier de Briey

Briey, , France

Site Status

Centre Medical de Bligny

Briis-sous-Forges, , France

Site Status

Centre hospitalier de Charleville Mezieres

Charleville-Mézières, , France

Site Status

Centre Hospitalier de Chalons-en-Champagne

Châlons-en-Champagne, , France

Site Status

Centre Hospitalier de Chateaubriant

Châteaubriant, , France

Site Status

Hopital Louis Pasteur

Colmar, , France

Site Status

Louis Mourier Hospital

Colombes, , France

Site Status

Centre Hospitalier Universitaire Henri Mondor

Créteil, , France

Site Status

Centre Hospitalier de Digne les Bains

Digne-les-Bains, , France

Site Status

Hopital Du Bocage

Dijon, , France

Site Status

Centre Hospitalier de Dreux

Dreux, , France

Site Status

Centre Hospitalier Intercommunal St. Aubin les Elbeuf

Elbeuf, , France

Site Status

Clinique Saint Vincent

Épernay, , France

Site Status

CHU de Grenoble - Hopital Michallon

Grenoble, , France

Site Status

Clinique Pasteur

Guilherand-Granges, , France

Site Status

Centre Hospitalier de Haguenau

Haguenau, , France

Site Status

Centre Hospitalier Departemental

La Roche-sur-Yon, , France

Site Status

Centre Hospitalier Universitaire de Bicetre

Le Kremlin-Bicêtre, , France

Site Status

Hopital Perpetuel Secours

Levallois-Perret, , France

Site Status

Hopital Robert Boulin

Libourne, , France

Site Status

Centre Hospital Universitaire Hop Huriez

Lille, , France

Site Status

Centre Hospital Regional Universitaire de Limoges

Limoges, , France

Site Status

Centre Hospitalier General

Longjumeau, , France

Site Status

Clinique Saint Jean

Lyon, , France

Site Status

Hopital Edouard Herriot - Lyon

Lyon, , France

Site Status

CHU de la Timone

Marseille, , France

Site Status

CHU Nord

Marseille, , France

Site Status

Centre Hospitalier de Martigues

Martigues, , France

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Centre Gray

Maubeuge, , France

Site Status

Centre Hospitalier de Meaux

Meaux, , France

Site Status

Centre Hospitalier General de Mont de Marsan

Mont-de-Marsan, , France

Site Status

Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle

Montpellier, , France

Site Status

CHU de Nancy - Hopitaux de Brabois

Nancy, , France

Site Status

Centre Hospitalier de Nevers

Nevers, , France

Site Status

Hopital de l'Archet CHU de Nice

Nice, , France

Site Status

C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau

Nîmes, , France

Site Status

Centre Hospitalier d'Orange

Orange, , France

Site Status

Hopital d'Instruction des Armees du Val de Grace

Paris, , France

Site Status

Hopital Europeen Georges Pompidou

Paris, , France

Site Status

Hopital Bichat - Claude Bernard

Paris, , France

Site Status

CHU Pitie-Salpetriere

Paris, , France

Site Status

Hopital Cochin

Paris, , France

Site Status

Hopital Tenon

Paris, , France

Site Status

Centre Hospitalier - Pau

Pau, , France

Site Status

Centre Hospitalier de Perpignan

Perpignan, , France

Site Status

Hopital Haut Leveque

Pessac, , France

Site Status

Hopital Rene Dubos

Pontoise, , France

Site Status

CHU - Robert Debre

Reims, , France

Site Status

Polyclinique De Courlancy

Reims, , France

Site Status

Centre Eugene Marquis

Rennes, , France

Site Status

Centre Hospitalier Universitaire de Rouen

Rouen, , France

Site Status

Pole Sante Sarthe et Loir Hopital Pierre Daguet

Sablé-sur-Sarthe, , France

Site Status

Centre Rene Huguenin

Saint-Cloud, , France

Site Status

Hopital d'Instruction des Armees Begin

Saint-Mandé, , France

Site Status

Centre Hospitalier de Saint-Quentin

Saint-Quentin, , France

Site Status

Center Hospitalier de Sens

Sens, , France

Site Status

Hopital Foch

Suresnes, , France

Site Status

Centre Hospitalier Valence

Valence, , France

Site Status

Nouvelle Clinique Generale

Valence, , France

Site Status

Centre Hospitalier de Valenciennes

Valenciennes, , France

Site Status

Centre Hospitalier Intercommunal de la Haute-Saone

Vesoul, , France

Site Status

Institut Gustave Roussy

Villejuif, , France

Site Status

Centre Hospitalier de Vire

Vire, , France

Site Status

Countries

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France

References

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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 elderly patients. [Abstract] J Clin Oncol 29 (Suppl 15): A-9111, 2011.

Reference Type RESULT

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] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-281, 2008.

Reference Type RESULT

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, Provencal J, Breysacher G, Legoux JL, Lepere C, Charneau J, Cretin J, Chone L, Azzedine A, Bouche O, Sobhani I, Bedenne L, Mitry E; FFCD investigators. Randomized phase III trial in elderly patients comparing LV5FU2 with or without irinotecan for first-line treatment of metastatic colorectal cancer (FFCD 2001-02). Ann Oncol. 2016 Jan;27(1):121-7. doi: 10.1093/annonc/mdv491. Epub 2015 Oct 20.

Reference Type RESULT
PMID: 26487578 (View on PubMed)

Aparicio T, Jouve JL, Teillet L, Gargot D, Subtil F, Le Brun-Ly V, Cretin J, Locher C, Bouche O, Breysacher G, Charneau J, Seitz JF, Gasmi M, Stefani L, Ramdani M, Lecomte T, Mitry E. Geriatric factors predict chemotherapy feasibility: ancillary results of FFCD 2001-02 phase III study in first-line chemotherapy for metastatic colorectal cancer in elderly patients. J Clin Oncol. 2013 Apr 10;31(11):1464-70. doi: 10.1200/JCO.2012.42.9894. Epub 2013 Mar 4.

Reference Type RESULT
PMID: 23460711 (View on PubMed)

Other Identifiers

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FFCD-2001-02

Identifier Type: -

Identifier Source: secondary_id

EU-20546

Identifier Type: -

Identifier Source: secondary_id

AVENTIS-FFCD-2001-02

Identifier Type: -

Identifier Source: secondary_id

PFIZER-FFCD-2001-02

Identifier Type: -

Identifier Source: secondary_id

CDR0000453855

Identifier Type: -

Identifier Source: org_study_id

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