IFCT-GFPC 05.02 A Randomized Phase III Trial Assessing in Patients With Advanced Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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The objective of this trial is to improve the duration of control disease for PS 0-1 patients who are not progressing on first-line cisplatin-gemcitabine chemotherapy. Standard therapy is for these patients to stop first-line chemotherapy after 4 to 6 cycles and to begin a second-line chemotherapy when progression of disease is occurring. Two approaches will be experimented in this trial in attempt to prolong progression free survival : Maintenance chemotherapy with single-agent gemcitabine continued till disease progression or toxicity. Sequential treatment with erlotinib immediately given after the end of first-line chemotherapy.

Official Title
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A Randomized Phase III Trial Assessing in Patients With Advanced Non-small Cell Lung Cancer Not Progressing on First Line Cisplatin-gemcitabine Chemotherapy Maintenance Chemotherapy With Gemcitabine or Sequential Treatment With Erlotinib

Conditions
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Stage IV Non-small Cell Lung Cancer

Intervention / Treatment
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* Drug: observation
* Drug: gemcitabine
* Drug: erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented NSCLC (tumor tissue samples will be provided to look for assessment of EGFR status with CISH, immunochemistry and mutations) : adenocarcinoma, squamous cell carcinoma, large cell carcinoma. A cytological documentation of NSCLC is accepted. Stage IV disease or metastatic relapse in not previously irradiated areas of a NSCLC previously treated with surgery or radiation therapy (with a histologically documented proof of relapse) or stage III B with documented pleural involvement. Measurable disease according to the RECIST criteria. Prior radiotherapy authorized except for irradiation concerning measurable disease. Age >18 and < 70 years. PS < 2. Normal hepatic function : serum bilirubin < 1.5 ULN, SGOT (ASAT) and SGPT (ALAT) < 2,5 ULN ; in presence of liver metastases, SGOT and SGPT must be < 5 x ULN. Creatinine clearance > 60 mL/min. Granulocyte count > 1,5 giga/L, platelet count > 100 giga/L. Life expectancy > 12 weeks. Written (signed) informed consent for use of tumors samples. Written (signed) informed consent to participate in the sudy. Exclusion Criteria: Small cell lung cancer, bronchiolo-alveolar carcinoma, neuro-endocrine carcinoma. PS > 1. Prior chemotherapy other than cisplatin-gemcitabine. Prior therapy with EGFR inhibitor (e.g. monoclonal antibody). No concomitant therapy with phenytoin, carbamazepine, rifampicine or phenobarbital. Concomitant radiotherapy except for localized bone irradiation. Symptomatic brain metastases. Superior vena cava syndrome. Any unstable systemic disease : significant cardiovascular disease including myocardial infarction within the previous year, active infection, significant hepatic or renal disease. Pre-existing interstitial lung disease. Any inflammatory changes of the surface of the eyes. Psychiatric disease with inability to understand the study or to comply with follow-up procedures. Grade > or = 2 peripheral neuropathy. Any other malignancies within 5 years (except for treated carcinoma in situ of the cervix or basal cell skin cancer). Pregnant or lactating women ; patients with reproductive potential must use effective contraception. Inability to comply with follow-up procedures.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: A (supervision)<br>medical supervision, second line chemotherapy if progression | Drug: observation<br>* observation, second line chemotherapy if progression<br>|
| Active Comparator: B (gemcitabicine)<br>Maintenance treatment (gemcitabicine 1250 mg/m² J1, J8 (repeated cycles every 21 days), second line chemotherapy if progression | Drug: gemcitabine<br>* 1250 mg/m² D1, D8 q21 days<br>|
| Experimental: C (Erlotinib)<br>Treatment by erlotinib 150 mg/day (sequential treatment), second line chemotherapy if progression | Drug: erlotinib<br>* 150 mg daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression free survival since randomization |  | time until progression | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival, |  | no time limit | 
| toxicity (NCIC-CTC 3.0), |  | time until progression | 
| quality of life (as assessed by LCSS). |  | until progression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer ;, metastatic ;, chemotherapy ;, erlotinib