Clinical trial NCT00303771: Combination Chemotherapy as First-Line Therapy in Treating Older Patients With Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: adenocarcinoma of the rectum
stage IV rectal cancer
stage IV colon cancer
adenocarcinoma of the colon
recurrent colon cancer
recurrent rectal cancer
Lead sponsor: Federation Francophone de Cancerologie Digestive
Sponsor class: OTHER
First posted: 2006-03-17
Enrollment: 282
Sex: ALL
Minimum age (years): 75
Maximum age (years): 120
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 .

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Progression Free Survival (survie sans progression)
timeFrame: 2011
Secondary outcomes:
measure: Overall Survival (survie globale)
timeFrame: 2011
Other outcomes:
Locations:
city: Abbeville
country: France
facility: Centre Hospitalier d'Abbeville
city: Agen
country: France
facility: Centre Hospitalier D'Agen
city: Alencon
country: France
facility: Centre hospitalier d'Alencon
city: Ales
country: France
facility: Clinique De Rochebelle
city: Amiens
country: France
facility: Centre Hospitalier Universitaire d'Amiens
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Avignon
country: France
facility: Institut Sainte Catherine
city: Avignon
country: France
facility: Hopital Duffaut
city: Blois
country: France
facility: Centre Hospitalier de Blois
city: Bordeaux
country: France
facility: Hopital Saint Andre
city: Boulogne Sur Mer
country: France
facility: Centre Hospitalier Docteur Duchenne
city: Boulogne-Billancourt
country: France
facility: Hopital Ambroise Pare
city: Bourg En Bresse
country: France
facility: C.H. Bourg En Bresse
city: Bourgoin-Jallieu
country: France
facility: Centre Hospitalier Pierre Oudot
city: Briey
country: France
facility: Centre Hospitalier de Briey
city: Briis-Sous-Forges
country: France
facility: Centre Medical de Bligny
city: Chalons-en-Champagne
country: France
facility: Centre Hospitalier de Chalons-en-Champagne
city: Charleville-Mezieres cedex
country: France
facility: Centre hospitalier de Charleville Mezieres
city: Chateaubriant cedex
country: France
facility: Centre Hospitalier de Chateaubriant
city: Colmar
country: France
facility: Hopital Louis Pasteur
city: Colombes Cedex
country: France
facility: Louis Mourier Hospital
city: Creteil
country: France
facility: Centre Hospitalier Universitaire Henri Mondor
city: Digne Cedex
country: France
facility: Centre Hospitalier de Digne les Bains
city: Dijon
country: France
facility: Hopital Du Bocage
city: Dreux
country: France
facility: Centre Hospitalier de Dreux
city: Elbeuf
country: France
facility: Centre Hospitalier Intercommunal St. Aubin les Elbeuf
city: Epernay
country: France
facility: Clinique Saint Vincent
city: Grenoble
country: France
facility: CHU de Grenoble - Hopital Michallon
city: Guilherand Granges
country: France
facility: Clinique Pasteur
city: Haguenau
country: France
facility: Centre Hospitalier de Haguenau
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier Departemental
city: Le Kremlin Bicetre
country: France
facility: Centre Hospitalier Universitaire de Bicetre
city: Levallois
country: France
facility: Hopital Perpetuel Secours
city: Libourne
country: France
facility: Hopital Robert Boulin
city: Lille
country: France
facility: Centre Hospital Universitaire Hop Huriez
city: Limoges
country: France
facility: Centre Hospital Regional Universitaire de Limoges
city: Longjumeau
country: France
facility: Centre Hospitalier General
city: Lyon
country: France
facility: Clinique Saint Jean
city: Lyon
country: France
facility: Hopital Edouard Herriot - Lyon
city: Marseille
country: France
facility: CHU de la Timone
city: Marseille
country: France
facility: CHU Nord
city: Martigues
country: France
facility: Centre Hospitalier de Martigues
city: Maubeuge
country: France
facility: Centre Gray
city: Meaux
country: France
facility: Centre Hospitalier de Meaux
city: Mont-de-Marsan
country: France
facility: Centre Hospitalier General de Mont de Marsan
city: Montpellier
country: France
facility: Centre Regional de Lutte Contre le Cancer - Centre Val d'Aurelle
city: Nancy
country: France
facility: CHU de Nancy - Hopitaux de Brabois
city: Nevers
country: France
facility: Centre Hospitalier de Nevers
city: Nice
country: France
facility: Hopital de l'Archet CHU de Nice
city: Nimes
country: France
facility: C.H.U. de Nimes - Groupe Hospitals-Universitaire Caremeau
city: Orange
country: France
facility: Centre Hospitalier d'Orange
city: Paris
country: France
facility: Hopital d'Instruction des Armees du Val de Grace
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou
city: Paris
country: France
facility: Hopital Bichat - Claude Bernard
city: Paris
country: France
facility: CHU Pitie-Salpetriere
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital Tenon
city: Pau
country: France
facility: Centre Hospitalier - Pau
city: Perpignan
country: France
facility: Centre Hospitalier de Perpignan
city: Pessac
country: France
facility: Hopital Haut Leveque
city: Pontoise
country: France
facility: Hopital Rene Dubos
city: Reims
country: France
facility: CHU - Robert Debre
city: Reims
country: France
facility: Polyclinique De Courlancy
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Rouen
country: France
facility: Centre Hospitalier Universitaire de Rouen
city: Sable Sur Sarthe
country: France
facility: Pole Sante Sarthe et Loir Hopital Pierre Daguet
city: Saint Cloud
country: France
facility: Centre Rene Huguenin
city: Saint-Mande
country: France
facility: Hopital d'Instruction des Armees Begin
city: Saint-Quentin
country: France
facility: Centre Hospitalier de Saint-Quentin
city: Sens
country: France
facility: Center Hospitalier de Sens
city: Suresnes
country: France
facility: Hopital Foch
city: Valence
country: France
facility: Centre Hospitalier Valence
city: Valence
country: France
facility: Nouvelle Clinique Generale
city: Valenciennes
country: France
facility: Centre Hospitalier de Valenciennes
city: Vesoul
country: France
facility: Centre Hospitalier Intercommunal de la Haute-Saone
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Vire
country: France
facility: Centre Hospitalier de Vire
Study officials:
affiliation: Hopital Ambroise Pare
name: Emmanuel Mitry, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
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] American Society of Clinical Oncology 2008 Gastrointestinal Cancers Symposium, 25-27 January 2008, Orlando, FL. A-281, 2008.
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, 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.
citation: 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.