S0720: Adjuvant Therapy Based on Gene Expression in Stage IA and IB Non-Small Cell Lung Cancer

OBJECTIVES:

Primary

• To assess the feasibility of assigning adjuvant treatment based on tumoral RRM1 and ERCC1 gene expression in patients with complete surgical resection of stage IA (≥ 2 cm) or IB non-small cell lung cancer.

Secondary

• To estimate the collective 2-year disease-free survival of these patients.
• To assess the frequency and severity of toxicities resulting from the administration of cisplatin and gemcitabine hydrochloride.
• To explore, preliminarily, the relationship between RNA and protein expression of RRM1 and ERCC1, and the relationship between RRM1 and ERCC1 expression in the formalin-fixed and paraffin-embedded tumor specimens, and to generate results on in situ protein expression and other assays for genes involved in drug efficacy.
• To assess the analytical performance of the biomarker assay.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 treatment arms based on RRM1 and ERCC1 gene expression.

• Arm I (RRM1 ≥ 40 and ERCC1 ≥ 65): Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks.
• Arm II (RRM1 < 40 and/or ERCC1 < 65): Beginning within 84 days after surgery, patients receive gemcitabine hydrochloride IV over 30 minutes on days 1 and 8 and cisplatin IV over 30-90 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.

Tumor samples acquired at the time of surgery are analyzed by immunofluorescence-based automated quantitative analysis for in situ expression of RRM1 and ERCC1. If available, additional samples are assessed using RT-PCR and real-time quantitative PCR for RRM1 and ERCC1 expression levels; polymorphism analysis for RRM1 and ERCC1 expression at the protein level; and tissue microarray analysis of genes associated with DNA synthesis, damage repair, and drug efficacy.

After completion of study therapy, patients are followed every 6 months for up to 2 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed non-small cell lung cancer

• Stage IA (longest tumor diameter 2-3 cm) or stage IB disease
• Must have undergone preoperative CT scan of the chest (including the entire liver and adrenals) with IV contrast AND a whole body PET scan or a combined PET/CT scan with no evidence of N1, N2, N3, or M1 disease within 42 days prior to surgery
• A whole body PET scan or a combined PET/CT must be performed within 84 days

• Any finding on PET scan that clinically suggests N1, N2, N3, or M1 disease must have been cleared by further evaluation, including, but not limited to, any of the following:

• Ultrasonography, X-ray radiology, magnetic resonance imaging, or nuclear medicine imaging
• Completely resected (R0) disease by lobectomy, bilobectomy, or pneumonectomy performed by open thoracotomy or video-assisted thoracoscopic surgery within the past 35 days

• Completely excised primary lesion with negative gross and microscopic margins
• At least two mediastinal lymph node stations sampled
• Must have tumor tissue available from the surgical resection specimen AND agree to have treatment assignment determined by a gene expression analysis performed on that tissue

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• ANC ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 mg/dL
• Serum bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 1.5 times ULN
• Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 60 mL/min
• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer
• In situ cervical cancer
• Adequately treated stage I-II cancer from which the patient is currently in complete remission
• Any other cancer from which the patient has been disease-free for 5 years
• Willing to provide prior smoking history

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No prior systemic chemotherapy or biologic therapy for lung cancer
• No prior thoracic radiation therapy (RT) (including RT to the chest wall)
• No other concurrent investigational agents, chemotherapeutic agents, RT, or hormonal therapy

• Steroids administered for antiemesis, adrenal failure, or septic shock OR hormones administered for non-disease-related conditions (e.g., insulin for diabetes) allowed