First-Line Combination Chemotherapy in Treating Patients With Stage IIIB or Stage IV Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy 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) may kill more tumor cells. It is not yet known which combination chemotherapy regimen is most effective in treating non-small cell lung cancer. PURPOSE: This randomized phase II trial is comparing different combination chemotherapy regimens to see how well they work as first-line therapy in treating patients with stage IIIB or stage IV non-small cell lung cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: To assess treatment outcomes of adjuvant chemotherapy based on ERCC1 and RRM1 mRNA levels in patients with stage IIIB or IV non-small cell lung cancer. OUTLINE: Patients are randomized to 1 of 2 treatment arms. RNA is isolated from pretreatment biopsy samples and analyzed with reverse transcriptase-PCR (RT-PCR) assays to determine ERCC1 and RRM1 mRNA expression. Arm I: Patients receive standard chemotherapy comprising docetaxel IV and carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Arm II: Patients are treated according to ERCC1 and RRM1 mRNA expression levels as determined by RT-PCR. Genotype A1 (high ERCC1 and high RRM1 mRNA levels): Patients receive non-platinum doublet chemotherapy comprising docetaxel and vinorelbine ditartrate IV on days 1 and 15. Treatment repeats every 4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Genotype A2 (high ERCC1 and low RRM1 mRNA levels): Patients receive non-platinum doublet chemotherapy comprising gemcitabine hydrochloride IV and vinorelbine ditartrate IV on days 1 and 8. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Genotype B1 (low ERCC1 and high RRM1 mRNA levels): Patients receive platinum doublet chemotherapy comprising docetaxel IV and carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. Genotype B2 (low ERCC1 and low RRM1 mRNA levels): Patients receive platinum doublet chemotherapy comprising gemcitabine hydrochloride IV on days 1 and 8 and carboplatin IV on day 1. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Official Title
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Genotype-driven Treatment of Advanced Non-small Cell Lung Cancer Based on mRNA Expression of ERCC1 & RRM1 as First-line Chemotherapy

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: carboplatin
* Drug: docetaxel
* Drug: gemcitabine hydrochloride
* Drug: vinorelbine tartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically proven or radiologically and clinically suspected stage IIIB (with malignant pleural effusion) or IV non-small cell lung cancer Unresectable disease At least 1 measurable lesion (> 10 mm with spiral CT scan or > 20 mm with conventional CT scan) No symptomatic or untreated brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy > 12 weeks ANC ≥ 1,500/mm³ Hemoglobin > 9.0 g/dL Platelet count ≥ 100,000/mm³ AST and ALT < 2 times upper limit of normal (ULN) Bilirubin < 1.5 mg/dL Creatinine < 1.5 times ULN Not pregnant or nursing No serious uncontrolled systemic intercurrent illness, including any of the following: Acute myocardial infarction Uncontrolled arrhythmia Uncontrolled heart failure Sepsis Poorly controlled diabetes No other malignancy within the last 5 years, except for carcinoma in situ of the cervix or nonmelanomatous carcinoma of the skin PRIOR CONCURRENT THERAPY: At least 3 weeks since prior radiotherapy, including cranial irradiation At least 3 weeks since prior major surgery No prior systemic chemotherapy except adjuvant chemotherapy provided it was completed more than 12 months ago

Ages Eligible for Study
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Minimum Age: 18 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm I<br>Patients receive standard chemotherapy of docetaxel and carboplatin. | Drug: carboplatin<br>* Given intravenously<br>Drug: docetaxel<br>* Given intravenously<br>|
| Experimental: Arm II, Genotype A1<br>Patients receive docetaxel and vinorelbine ditartrate. | Drug: docetaxel<br>* Given intravenously<br>Drug: vinorelbine tartrate<br>* Given intravenously<br>|
| Experimental: Arm II, Genotype A2<br>Patients receive gemcitabine hydrochloride and vinorelbine ditartrate. | Drug: gemcitabine hydrochloride<br>* Given intravenously<br>Drug: vinorelbine tartrate<br>* Given intravenously<br>|
| Experimental: Arm II, Genotype B1<br>Patients receive docetaxel and carboplatin. | Drug: carboplatin<br>* Given intravenously<br>Drug: docetaxel<br>* Given intravenously<br>|
| Experimental: Arm II, Genotype B2<br>Patients receive gemcitabine hydrochloride and carboplatin. | Drug: carboplatin<br>* Given intravenously<br>Drug: gemcitabine hydrochloride<br>* Given intravenously<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial responses) |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate |  |  | 
| Response duration |  |  | 
| Progression-free survival |  |  | 
| Overall survival |  |  | 
| Toxicity |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIB non-small cell lung cancer, stage IV non-small cell lung cancer