Gemcitabine and Cisplatin in Treating Patients With Stage I Non-Small Cell Lung Cancer That Was Removed by Surgery - Full Text View

Sponsor:	Southwest Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00792701

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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II ERCC1 and RRM1-Based Adjuvant Therapy Trial in Patients With Stage I Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer Surgery

Drug Information available for: Cisplatin Gemcitabine Gemcitabine hydrochloride

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Feasibility of pharmacogenomics-based treatment assignment in the cooperative group setting [ Designated as safety issue: No ]

Secondary Outcome Measures:

Two-year disease-free survival [ Designated as safety issue: No ]
Frequency and severity of toxicities as assessed by NCI CTCAE v3.0 [ 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 [ Designated as safety issue: No ]
Generation of results on in situ protein expression and other assays for genes involved in drug efficacy [ Designated as safety issue: No ]
Analytical performance of the biomarker assay [ Designated as safety issue: No ]

Estimated Enrollment:	55
Study Start Date:	November 2008
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Arm I: No Intervention Patients undergo active monitoring after surgery with disease assessments at 8, 16, and 24 weeks.	Other: active surveillance Patients undergo active monitoring
Arm II: Experimental 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

Criteria

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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00792701

Show 174 Study Locations

Sponsors and Collaborators

Southwest Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	Ralph G. Zinner, MD	M.D. Anderson Cancer Center
Investigator:	Eric Vallieres, MD, FRCSC	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Southwest Oncology Group - Group Chair's Office ( Laurence H. Baker )
Study ID Numbers:	CDR0000625070, SWOG-S0720
Study First Received:	November 16, 2008
Last Updated:	February 4, 2010
ClinicalTrials.gov Identifier:	NCT00792701 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage I non-small cell lung cancer

Additional relevant MeSH terms:

Thoracic Neoplasms
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Neoplasms by Site
Cisplatin
Respiratory Tract Diseases
Lung Neoplasms
Therapeutic Uses

Gemcitabine
Respiratory Tract Neoplasms
Neoplasms by Histologic Type
Enzyme Inhibitors
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Radiation-Sensitizing Agents
Lung Diseases
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on February 08, 2010