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 anOptimized Strategy Allocating the Same Treatments

Study Overview
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Brief Summary
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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.

Conditions
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Non Small-cell Lung Cancer

Intervention / Treatment
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* Procedure: Dual-agent therapy or docetaxel alone or best supportive care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: dual-agent therapy or docetaxel alone<br>dual-agent therapy based on Carboplatin (Carboplatin-Pemetrexed for non epidermoid forms, Carboplatin-Gemcitabin for epidermoid forms) or Docetaxel alone, according to PS or age | |
| Experimental: dual-agent therapy or docetaxel or best supportive care<br>dual-agent therapy based on Carboplatin (Carboplatin-Pemetrexed for non epidermoid forms, Carboplatin-Gemcitabin for epidermoid forms) or Docetaxel alone, or best supportive care, allocated on the basis of a simplified geriatric scale, plus a more thorough geriatric evaluation if necessary | Procedure: Dual-agent therapy or docetaxel alone or best supportive care<br>* ARM B: (245 patients) Treatment if the SGS screening test is negative: non epidermoid tumor: Carboplatin ® AUC 5 on D1 and Alimta ®(pemetrexed) 500 mg/m² D1, D1=D21 with vitamin B9 and B12 supplementation. Maximum of four 3-week cycles. epidermoid tumor: Carboplatin AUC 5 on D1 and Gemcitabin 1000 mg/m² on D1 and D8, D1=D21. Treatment if SGS screening test is positive (cf.table 1): Vulnerable subjects will receive: Taxotere ® (Docetaxel) 38 mg/m² on D1 and D8, D1=D21. Maximum of four 3-week cycles Fragile subjects are patients considered to be at a high risk of complications during chemotherapy; they will therefore receive best supportive care (BSC) with appropriate geriatric management.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | date of documented progression up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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