S0720: Adjuvant Therapy Based on Gene Expression in Stage IA and IB Non-Small Cell Lung Cancer
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lung Cancer |
Drug: cisplatin Drug: gemcitabine hydrochloride Other: active surveillance |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: 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 maximum of 2 years ] [ Designated as safety issue: No ]
- Two-year disease-free survival [ Time Frame: From time of registration to maximum of 2 years ] [ Designated as safety issue: No ]
- Frequency and severity of toxicities as assessed by NCI CTCAE v3.0 [ Time Frame: From time of registration to maximum of 2 years ] [ Designated as safety issue: Yes ]
- Relationship between RNA and protein expression of RRM1 and ERCC1 and 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Analytical performance of the biomarker assay [ Time Frame: From time of registration to maximum of 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 55 |
| Study Start Date: | November 2008 |
| Estimated Primary Completion Date: | June 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Active Comparator: Arm I
Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks.
|
Other: active surveillance
Patients undergo active monitoring
|
|
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.
|
Drug: cisplatin
Given IV
Drug: gemcitabine hydrochloride
Given IV
|
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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
Contacts and Locations
Show 147 Study Locations| Study Chair: | Ralph G. Zinner, MD | M.D. Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | Southwest Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00792701 History of Changes |
| Other Study ID Numbers: | CDR0000625070, S0720, U10CA032102 |
| Study First Received: | November 16, 2008 |
| Last Updated: | January 30, 2013 |
| Health Authority: | United States: Federal Government |
Keywords provided by Southwest Oncology Group:
|
stage I non-small cell lung cancer |
Additional relevant MeSH terms:
|
Carcinoma, Non-Small-Cell Lung Lung Neoplasms Carcinoma, Bronchogenic Bronchial Neoplasms Respiratory Tract Neoplasms Thoracic Neoplasms Neoplasms by Site Neoplasms Lung Diseases Respiratory Tract Diseases Gemcitabine Cisplatin Antineoplastic Agents |
Therapeutic Uses Pharmacologic Actions Radiation-Sensitizing Agents Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors |
ClinicalTrials.gov processed this record on June 13, 2013