Clinical trial NCT01257139: Trial Involving Subjects Over 70 Years of Age With Non Small-cell Lung Cancer of Stage IV and Comparing a "Classical" Strategy of Treatment Allocation, With an"Optimized" Strategy Allocating the Same Treatments
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Small-cell Lung Cancer
Keywords: To evaluate a geriatric scale designed to help with treatment
allocation to dual-agent therapy based on platinum or to
single-agent chemotherapy in elderly subjects with advancedstage
NSCLC, based on the time to failure in the two arms
Lead sponsor: Rennes University Hospital
Sponsor class: OTHER
First posted: 2010-12-09
Enrollment: 490
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: This is a phase III randomized multicenter study involving subjects over 70 years of age with non small-cell lung cancer of IV and a PS of 0, 1 or 2, who have not previously received chemotherapy. The aim is to validate the use of a simplified geriatric scale (SGS) as a screening tool. If the SGS results are normal, the patient will be treated with dual-agent therapy based on platinum (carboplatin + pemetrexed if the histology is non epidermoid, carboplatin + gemcitabin if the histology is epidermoid), with no further geriatric assessment. When the SGS reveals abnormalities, a comprehensive geriatric evaluation (CGE) will be used to define two subpopulations on Balducci's fragility scale, who will receive either monotherapy (docetaxel) or best supportive care.

The strategy based on the SGS will be compared with a treatment algorithm based on standard criteria (PS and age), with no specific geriatric assessment. The main endpoint is the time to treatment failure. The SGS is composed of the Charlson co-morbidity scale, functional assessment based on PS, Katz' ADL scale, Lawton's simplified IADL scale, simplified cognitive assessment with the mini-MMSE according to Schultz-Larsen, a geriatric depression scale (GDS 5), and screening for a geriatric syndrome defined by the existence of dementia, repeated falls, and urinary and fecal incontinence. The SGS will be validated by comparison with the CGE, that will be administered systematically at enrollment. All the SGS items are included in the CGE.

Secondary endpoints will be quality of life (measured with the LCSS and EuroQoL questionnaires), overall survival, the objective response rate, and toxicity. The investigators will also study the predictive power of nutritional indices such as the PINI and the Buzby score with respect to survival, the treatment response, and tolerability.


Eligibility criteria: Inclusion Criteria:

* Cytologically or histologically proven NSCLC(adenocarcinoma, epidermoid carcinoma, large-cell carcinoma) of stage IV with histologically or cytologically proven pleurisy or neoplastic pericarditis.
* No previous systemic chemotherapy for lung cancer.
* Presence of at least one measurable target lesion (RECIST rules) in a non irradiated region.
* Age strictly at least 70 years.
* PS 0, 1 or 2.
* Life expectancy sup 12 weeks.
* Creatinine clearance at least 45 ml per min with MDRD Formula (Modification in the Diet in Renal Disease).
* Normal hematologic function: absolute polymorphonuclear neutrophil count \> 1.5 . 109 per l and or platelets sup 100 . 109/l, hemoglobin sup 9.5 g per dl
* Normal hepatic function: bilirubin inf 1.5 x normal, SGOT and SGPT inf 2.5 . normal.
* Patients with metastatic relapse (cytologically or histologically proven) of primary lung cancer in a non irradiated region, after surgical excision or local external radiotherapy.
* Prior irradiation is authorized if it involved less than 25 percent of the total bone marrow volume.
* Men must be surgically sterile or must accept the use of an effective contraceptive methodall along and until 6 months after the treatment period
* Signed written informed consent.

Exclusion Criteria:

* Other severe concurrent disorders that occurred during the prior six months before enrollment (myocardial infection, severe or unstable angor, coronarian or peripheric arterial bypass operation, NYHA class 3 or 4 congestive heart failure, transient or constituted cerebral ischemic attack, at least grade 2 peripheral neuropathy, stomach ulcer, erosive oesophagitis or gastritis, psychiatric or neurological disorders preventing the patient from understanding the trial, uncontrolled infections).
* Another previous or concomitant cancer, except for basocellular cancer of the skin or treated cervical cancer in situ, or appropriately treated localized lowgrade prostate cancer (Gleason score inf 6), unless the initial tumor was diagnosed and definitively treated more than 5 years previously, with no evidence of relapse.
* Bronchoalveolar or neuroendocrine or composite cancers
* Superior caval syndrome.
* Presence of symptomatic brain metastases.
* Peripheral neuropathies (grade sup 2).
* Performance status sup 2 (ECOG).
* A significant third liquid part (for example ascitis or pleural effusion) hat can't be controlled with drainage or other procedures before enrollment
* Impossibility to stop a treatment by aspirin (if the dose is more than 1.3 mg per day) or NSAI during 5 days (8 days for molecules with long period action like piroxicam
* Concurrent participation in another clinical trial.
* Definitive contraindication to steroids or folic acid and vitamin B12 if histology is non-epidermoid.
* All concurrent radiotherapy, except for local palliative bone radiotherapy.
* Concurrent administration of one or several other antitumor therapies. Recent vaccination for yellow fever (during the 30 days before enrollment)
* Psychological, familial, social or geographic difficulties preventing follow-up as defined by the protocol.
* Administrative or legal detention.
* Contraindication to the study drugs.
* Concurrent participation in another clinical trial

Primary outcomes:
measure: Time to failure Defined from the date of inclusion to the date of documented progression Or death of any cause Or trial exit for toxicity considered unacceptable by the patient or by the investigator Or withdrawal of consent
timeFrame: date of documented progression up to 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Aix en Provence
country: France
facility: CH du Pays d'Aix
city: Amiens
country: France
facility: CHU Amien Picardie
city: Angers
country: France
facility: Centre Hospitalier Universitaire d'Angers
city: Annecy
country: France
facility: Centre Hospitalier d'Annecy
city: Antibes
country: France
facility: Centre Hospitalier Général de la Fontonne Antibes
city: Bastia
country: France
facility: CH de Bastia
city: Beauvais
country: France
facility: Centre Hospitalier de Beauvais
city: Bordeaux Pessac
country: France
facility: CHU Bordeaux Hôpital Haut Lévêque
city: Brest
country: France
facility: Centre Hospitalier Universaitaire de Brest
city: Brest
country: France
facility: HIA Tonnerre
city: Caen
country: France
facility: Centre François Baclesse
city: Cergy Pontoise
country: France
facility: CH René Dubos - Pontoise
city: Charleville Mézières
country: France
facility: Centre Hospitalier Charleville mézières
city: Créteil
country: France
facility: CHI Créteil
city: Draguignan
country: France
facility: Centre hospitalier de Draguignan
city: Elbeuf
country: France
facility: Centre Hospitalier de Elbeuf
city: Gap
country: France
facility: CH Gap
city: La Roche sur Yon
country: France
facility: CH La Roche sur Yon
city: Le Chesnay
country: France
facility: Hôpital A Mignot Le Chesnay
city: Lille
country: France
facility: Centre Omar Lambret
city: Limoges
country: France
facility: Hôpital du Cluzeau
city: Longjumeau
country: France
facility: CHR Longjumeau
city: Lorient
country: France
facility: Centre Hospitalier de Bretagne Sud
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Mantes La Jolie
country: France
facility: Centre Hospitalier
city: Marseille
country: France
facility: Hôpital Sainte Marguerite
city: Marseille
country: France
facility: Institut Paoli-Calmette
city: Martigues
country: France
facility: Centre Hospitalier
city: Meaux
country: France
facility: Hôpital Saint Farron
city: Mulhouse
country: France
facility: Centre Hospitalier de Mulhouse
city: Orléans
country: France
facility: CHR Orléans
city: Paris
country: France
facility: Paris Hôpital saint Antoine
city: Perpignan
country: France
facility: Centre Catalan
city: Périgueux
country: France
facility: Centre Hospitalier de Périgueux
city: Rennes
country: France
facility: Rennes Hospital University
city: Rouen
country: France
facility: CHU Rouen Hôpital Boisguillaume
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: saint Brieuc
country: France
facility: Hôpital Yves Le Foll
city: Saint Etienne
country: France
facility: CHU Saint Etienne - Hôpital Nord
city: Salon de Provence
country: France
facility: Centre Hospitalier Général Salon de Provence
city: St Priest en Jarez
country: France
facility: Institut de Cancérologie de la Loire
city: Toulon Naval
country: France
facility: Hôpital d'Instruction des Armées
city: Toulon
country: France
facility: Hôpital Font-Pre
city: Toulouse
country: France
facility: CHU Touloues
city: Villefranche sur Saone
country: France
facility: Centre Hospitalier De Villefranche sur Saone
Study officials:
References:
citation: Corre R, Greillier L, Le Caer H, Audigier-Valette C, Baize N, Berard H, Falchero L, Monnet I, Dansin E, Vergnenegre A, Marcq M, Decroisette C, Auliac JB, Bota S, Lamy R, Massuti B, Dujon C, Perol M, Daures JP, Descourt R, Lena H, Plassot C, Chouaid C. Use of a Comprehensive Geriatric Assessment for the Management of Elderly Patients With Advanced Non-Small-Cell Lung Cancer: The Phase III Randomized ESOGIA-GFPC-GECP 08-02 Study. J Clin Oncol. 2016 May 1;34(13):1476-83. doi: 10.1200/JCO.2015.63.5839. Epub 2016 Feb 16.