Chemotherapy or Observation in Treating Patients With Early Stage Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as vinorelbine, cisplatin, docetaxel, gemcitabine, and pemetrexed disodium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes after surgery, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether chemotherapy is more effective than observation in treating patients who have undergone surgery for stage I non-small cell lung cancer. PURPOSE: This randomized phase III trial is studying four chemotherapy regimens to see how well they work compared with observation in treating patients with early stage non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary To determine the potential overall survival benefit of adjuvant chemotherapy in patients with early stage non-small cell lung cancer (NSCLC) randomized to chemotherapy compared to those randomized to the present standard of care (observation). To collect and process high-quality fresh frozen lung cancer tumor tissue for gene expression array generation from multiple institutions. Secondary To evaluate selected genomic-based lung cancer prognostic models using data from the patients randomized to observation after resection. To characterize the rate of chemotherapy toxicity for the different chemotherapy treatment regimens. To assess quality of life (QOL) in early stage patients periodically after resection for NSCLC. To examine the impact of chemotherapy on QOL for patients receiving chemotherapy, as compared to patients in the observation arm. OUTLINE: This is a multicenter study. Patients are stratified according to pathologic stage (I vs II) and ECOG performance status (0 vs 1). Patients are randomized to 1 of 2 treatment arms within 12 weeks after surgery. All patients undergo complete resection of disease (i.e., lobectomy, sleeve lobectomy, bi-lobectomy, or pneumonectomy, but not segmentectomy or wedge resection). Arm I: Patients receive 1 of 3 chemotherapy regimens. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Regimen 1: Patients receive vinorelbine ditartrate IV over 10 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1. Regimen 2: Patients receive docetaxel IV over 60 minutes and cisplatin IV over 60 minutes on day 1. Regimen 3: Patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 60 minutes on day 1. Regimen 4: Patients receive pemetrexed disodium IV over 10 minutes and cisplatin IV over 60 minutes on day 1. Arm II: Patients receive standard care (observation). Tissue obtained at surgery is examined by RNA microarray analysis. A Lung Metagene Score (LMS) is determined for each patient and correlated with survival and response. After completion of study treatment, patients are followed every 6 months for 5 years and then once a year for 7 years.

Official Title
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A Randomized Phase III Trial of Adjuvant Chemotherapy in Patients With Early Stage Non-Small Cell Lung Cancer Associated With Banking of Frozen Tumor Specimens and Collection of Gene Expression Profile Data

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: docetaxel
* Drug: gemcitabine hydrochloride
* Drug: pemetrexed disodium
* Drug: vinorelbine tartrate
* Procedure: standard follow-up care


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-small cell lung cancer Any variant allowed (e.g., pure or mixed bronchioloalveolar carcinoma or adenosquamous cell carcinoma) Primary tumor must be T1a, T1b, T2a, or T2b by AJCC 7.0 No status Tumor measuring ≥ 2.0 cm but ≤ 7.0 cm in diameter by CT scan The mass must have a source document to verify tumor size in the greatest dimension, which includes a CT scan report, a clinic note from the enrolling physician, and/or a printed image with caliper measurements on the lung mass Node-negative disease Evidence of hilar or mediastinal node involvement by chest CT scan (> 1 cm diameter) must be assessed with mediastinoscopy, endo-esophageal ultrasound with biopsy, endo-bronchial ultrasound, bronchoscopy, or mediastinal nodal sampling before or at time of thoracotomy No locally advanced or metastatic disease PATIENT CHARACTERISTICS: ECOG performance status 0-1 Granulocytes ≥ 1,500/μL Platelet count ≥ 100,000/μL Bilirubin ≤ 1.5 mg/dL AST < 1.5 times upper limit of normal (ULN) Serum creatinine ≤ 1.5 times ULN Not pregnant or nursing Fertile patients must use effective contraception No history of prior or concurrent malignancy, except curatively treated carcinoma in situ of the cervix, basal cell or squamous cell carcinoma of the skin, surgically treated in situ carcinoma of the breast, or other cancer for which the patient has been disease-free for 3 years PRIOR CONCURRENT THERAPY: More than 3 years since prior cytotoxic or anticancer treatment No concurrent treatment with hormones or other chemotherapeutic agents, except steroids given for adrenal failure, hormone administered for nondisease-related conditions (e.g., insulin for diabetes), or intermittent use of dexamethasone as an antiemetic No concurrent thoracic radiotherapy

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
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive cisplatin IV on day 1 and vinorelbine ditartrate IV on days 1 and 8 OR docetaxel IV and cytarabine IV on day 1 OR gemcitabine hydrochloride IV on days 1 and 8 and cytarabine IV on day 1 OR pemetrexed disodium IV and cisplatin IV on day 1.. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. | Drug: cisplatin<br>* Given IV<br>Drug: docetaxel<br>* Given IV<br>Drug: gemcitabine hydrochloride<br>* Given IV<br>Drug: pemetrexed disodium<br>* Given IV<br>Drug: vinorelbine tartrate<br>* Given IV<br>|
| Experimental: Arm II<br>Patients receive standard care (observation). | Procedure: standard follow-up care<br>* Standard care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival (OS) is defined as the time between formal registration and death from any cause. The median OS with 95% CI was estimated using the Kaplan-Meier method. | Up to 12 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IA non-small cell lung cancer, stage IB non-small cell lung cancer, stage IIA non-small cell lung cancer, adenocarcinoma of the lung, adenosquamous cell lung cancer, bronchoalveolar cell lung cancer, large cell lung cancer, squamous cell lung cancer