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

Phase 2
Completed
Conditions
Lung Cancer
Interventions
Registration Number
NCT00792701
Lead Sponsor
SWOG Cancer Research Network
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
85
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Arm IIgemcitabine hydrochlorideBeginning 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.
Arm IIcisplatinBeginning 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.
Primary Outcome Measures
NameTimeMethod
Feasibility of Pharmacogenomics-based Treatment Assignment in the Cooperative Group SettingFrom 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.

Secondary Outcome Measures
NameTimeMethod
Two-year Disease-free SurvivalFrom time of registration to maximum of 2 years
Relationship Between RRM1 and ERCC1 Expression in the Formalin-fixed and Paraffin-embedded Tumor Specimens.From time of registration to maximum of 2 years

RRM1 and ERCC1 protein levels are expressed as a simple score with no units.

Frequency and Severity of Toxicities as Assessed by NCI CTCAE v3.0From time of registration to maximum of 2 years

Patients in the active monitoring arm were not followed for adverse events.

Trial Locations

Locations (147)

Hembree Mercy Cancer Center at St. Edward Mercy Medical Center

🇺🇸

Fort Smith, Arkansas, United States

City of Hope Comprehensive Cancer Center

🇺🇸

Duarte, California, United States

Tibotec Therapeutics - Division of Ortho Biotech Products, LP

🇺🇸

Marysville, California, United States

Valley Medical Oncology Consultants - Pleasanton

🇺🇸

Pleasanton, California, United States

Sutter Cancer Center at Roseville Medical Center

🇺🇸

Roseville, California, United States

Sutter Cancer Center

🇺🇸

Sacramento, California, United States

University of California Davis Cancer Center

🇺🇸

Sacramento, California, United States

Tahoe Forest Cancer Center

🇺🇸

Truckee, California, United States

Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center

🇺🇸

Hartford, Connecticut, United States

Northeast Georgia Medical Center

🇺🇸

Gainesville, Georgia, United States

Scroll for more (137 remaining)
Hembree Mercy Cancer Center at St. Edward Mercy Medical Center
🇺🇸Fort Smith, Arkansas, United States

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