Surgery, Gemcitabine, Cisplatin, and Radiation Therapy in Treating Patients With Stage II or Stage III Non-Small Cell Lung Cancer

NCT ID: NCT00530634

Last Updated: 2015-10-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-08-31
• Study Completion Date: 2013-06-30

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 more than one drug (combination chemotherapy) together with radiation therapy after surgery may kill any tumor cells that remain after surgery.

PURPOSE: This phase II trial is studying how well surgery followed by gemcitabine, cisplatin, and radiation therapy works in treating patients with stage II or stage III non-small cell lung cancer.

Detailed Description

OBJECTIVES:

• To assess overall survival and progression-free survival of patients with stage II-IIIB non-small cell lung cancer undergoing surgical resection, followed by adjuvant chemotherapy comprising gemcitabine and cisplatin, and radiotherapy.
• To assess the toxicities of this regimen in these patients.
• To evaluate the mRNA expression of enzymes (i.e., excision repair cross complementing protein, ribonucleotide reductase, and cytidine/deoxycytidine deaminase and kinase), which may be important in regulating the cytotoxicity of gemcitabine and cisplatin in patient tumors.
• To correlate mRNA levels with progression-free survival of patients treated with this regimen.
• To assess BCL2, P53, and HER2-neu expression by IHC and correlation with progression-free survival.

OUTLINE: Patients undergo surgical resection of their tumor and mediastinal lymph node dissection. Patients with complete surgical eradication of their disease or pathologic evidence of microscopic residual disease proceed to adjuvant chemotherapy.

Within approximately 60 days after surgical resection, patients receive adjuvant chemotherapy comprising gemcitabine IV over 30 minutes on days 1 and 8 and cisplatin IV over 1 hour on day 8. Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Beginning 130-144 days after surgery, patients undergo radiotherapy once daily, five days a week, for approximately 6 weeks.

Tumor tissue specimens are obtained at the time of surgical resection for pharmacodynamic and biomarker correlative studies. Specimens are examined by reverse transcriptase-polymerase chain reaction to measure mRNA expression of target oncogenes (i.e., DNA repair gene ERCC-1 and M2 subunit of the DNA repair gene ribonucleotide reductase) and enzymes (i.e., cytidine/deoxycytidine deaminase and kinase). Resected specimens are also assessed by IHC for the expression of BCL2, P53, and HER2-neu genes.

After completion of study therapy, patients are followed every 6 months for 5 years and annually thereafter.

Conditions

Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Gemcitabine + Cisplatin

Surgical resection followed by (within 60 days) by chemotherapy (Gemcitabine at 1000 mg/m2 IV over 30 minutes on days 1 and 8 of a 21 day cycle and Cisplatin at 75 mg/m2 IV over 1 hour on day 8 of a 21 day cycle) followed by radiation therapy (treated using linear accelerator with photon beam energy of 6-21 MV) upon completion of 3 cycles of chemotherapy.

Group Type: EXPERIMENTAL

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

gene expression analysis

Intervention Type: GENETIC

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

immunohistochemistry staining method

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Interventions

cisplatin

Intervention Type: DRUG

gemcitabine hydrochloride

Intervention Type: DRUG

gene expression analysis

Intervention Type: GENETIC

reverse transcriptase-polymerase chain reaction

Intervention Type: GENETIC

immunohistochemistry staining method

Intervention Type: OTHER

adjuvant therapy

Intervention Type: PROCEDURE

conventional surgery

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed single, primary bronchogenic non-small cell lung cancer meeting the following subtypes:

• Adenocarcinoma (no bronchioalveolar cell histology)
• Squamous cell carcinoma
• Large cell carcinoma
• Meeting the following staging criteria:

• Stage IIB (T2, N1, M0, or T3, N0, M0)
• Stage IIIA (T1-3, N2, M0 or T3, N1, M0)
• Stage IIIB (Any T, N3, M0 or T4, Any N, M0)
• No more than 1 parenchymal lesion in the same lung or in both lungs
• No tumor involving the superior sulcus (e.g., Pancoast tumor)
• Patients must undergo evaluation by the involved thoracic surgeon, medical oncologist, and radiation oncologist prior to registration
• No evidence of metastatic disease

• Biopsy or aspiration cytology required to confirm the benign diagnosis of CT or MRI abnormalities that potentially represent metastatic disease
• Biopsy required if all noninvasive tests are indeterminant

PATIENT CHARACTERISTICS:

• Karnofsky performance status 70-100%
• Absolute granulocyte count ≥ 1,500/μL
• Platelet count ≥ 100,000/μL
• Bilirubin ≤ 3 times upper limit of normal (ULN)
• SGOT and SGPT ≤ 3 times ULN
• Creatinine clearance > 50 mL/min
• No prior malignancy except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, ductal or lobular carcinoma in situ of the breast, or any other cancer from which the patient has been disease-free for 5 years
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective protection
• No significant hearing loss or patient unwilling to accept potential for further hearing loss
• No uncontrolled medical illness by appropriate medical therapy (e.g., myocardial infarction within the past 3 months or liver cirrhosis)
• No symptomatic peripheral neuropathy affecting activities of daily living

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or radiotherapy for lung cancer

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marianna Koczywas, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Comprehensive Cancer Center

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-99077

Identifier Type: -

Identifier Source: secondary_id

CDR0000564760

Identifier Type: REGISTRY

Identifier Source: secondary_id

99077

Identifier Type: -

Identifier Source: org_study_id