S0720: Adjuvant Therapy Based on Gene Expression in Stage IA and IB Non-Small Cell Lung Cancer
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.
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase II ERCC1 and RRM1-Based Adjuvant Therapy Trial in Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)|
- Feasibility of Pharmacogenomics-based Treatment Assignment in the Cooperative Group Setting [ Time Frame: From time of registration to 84 days after surgical resection. ]Feasibility will be assessed both by accrual rate and the percentage of patients successfully assigned to adjuvant chemotherapy or active monitoring.
- Two-year Disease-free Survival [ Time Frame: From time of registration to maximum of 2 years ]
- Frequency and Severity of Toxicities as Assessed by NCI CTCAE v3.0 [ Time Frame: From time of registration to maximum of 2 years ]Patients in the active monitoring arm were not followed for adverse events.
- Relationship Between RRM1 and ERCC1 Expression in the Formalin-fixed and Paraffin-embedded Tumor Specimens. [ Time Frame: From time of registration to maximum of 2 years ]RRM1 and ERCC1 protein levels are expressed as a simple score with no units.
- Analytical Performance of the Biomarker Assay [ Time Frame: From time of registration to maximum of 2 years ]
- Generation of Results on in Situ Protein Expression and Other Assays for Genes Involved in Drug Efficacy [ Time Frame: From time of registration to maximum of 2 years ]
- Relationship Between RNA and Protein Expression of RRM1 and ERCC1 [ Time Frame: From time of registration to maximum of 2 years ]
|Study Start Date:||November 2008|
|Study Completion Date:||April 2016|
|Primary Completion Date:||April 2016 (Final data collection date for primary outcome measure)|
Experimental: Arm II
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.
Given IVDrug: gemcitabine hydrochloride
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00792701
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|Study Chair:||Ralph G. Zinner, MD||M.D. Anderson Cancer Center|