S0720: Adjuvant Therapy Based on Gene Expression in Stage IA and IB Non-Small Cell Lung Cancer
Condition: Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Study type: Interventional
Phase: Phase 2

Summary: 
      RATIONALE: Drugs used in chemotherapy, such as gemcitabine and cisplatin, work in different
      ways to stop the growth of tumor cells, either by killing the cells or by stopping them from
      dividing. Giving chemotherapy drugs after surgery may kill any tumor cells that remain after
      surgery. Sometimes, after surgery, the tumor may not need more treatment until it progresses.
      In this case, observation may be sufficient.

      PURPOSE: This phase II trial is studying how well giving gemcitabine together with cisplatin
      works in treating patients with stage I non-small cell lung cancer that was removed by
      surgery.
    

Detailed description: 
      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.
    

Intervention name(s): cisplatin; gemcitabine hydrochloride
Intervention type(s): Drug; Drug
Intervention description(s): Given IV; Given IV
Intervention MeSH terms: Gemcitabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: stage I non-small cell lung cancer