Pemetrexed Disodium and Cisplatin in Treating Patients Who Are Undergoing Surgery for Stage I, Stage II, or Stage III Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as pemetrexed disodium 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) and giving them before and after surgery may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving pemetrexed disodium and cisplatin before and after surgery works in treating patients with stage I, stage II, or stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Determine the pathologic complete response in patients with stage IB-IIIB non-small cell lung cancer treated with neoadjuvant chemotherapy comprising pemetrexed disodium and cisplatin followed by surgery and adjuvant pemetrexed disodium and cisplatin. Secondary Determine the adverse events of this regimen in these patients. Determine the overall and disease-free survival of patients treated with this regimen. Correlate response with the presence or absence of ERCC1 and DHFR, thymidylate synthase, DPD, and GARFT in patients treated with this regimen. Correlate the fragile site on chromosome 12 within the SMRT gene with metastasis after definitive treatment with this regimen in these patients. OUTLINE: Neoadjuvant chemotherapy: Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over approximately 1 hour on day 1. Treatment repeats every 21 days for 3 courses. Patients are then evaluated for disease resectability. Patients with no evidence of disease progression proceed to thoracotomy within the next 28-48 days. Thoracotomy: Patients found to have unresectable disease during thoracotomy receive further treatment off study. Patients with resectable disease undergo complete surgical resection of the tumor. Forty to eighty days later, patients proceed to adjuvant chemotherapy. Adjuvant chemotherapy: Patients receive pemetrexed disodium and cisplatin as before for 2 courses. Patients with progressive disease after completion of neoadjuvant chemotherapy are followed every 6 months. All other patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. PROJECTED ACCRUAL: A total of 38 patients will be accrued for this study over 6.5 years.

Official Title
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Molecular and Genetic Changes in Patients With Resectable Non-Small Cell Lung Cancer (NSCLC) Following Neoadjuvant Chemotherapy With Cisplatin and Alimta - Phase II Study

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: cisplatin
* Drug: pemetrexed disodium
* Procedure: adjuvant therapy
* Procedure: conventional surgery
* Procedure: neoadjuvant therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Microscopically confirmed non-small cell lung cancer Stage IB (T2, N0, M0), IIA (T1, N1, M0), IIB (T2, N1, M0 or T3, N0, M0), or IIIA (T1-3, N1-2, M0) disease Satellite lesions in one lobe (T4) (stage IIIB) allowed Meets 1 of the following criteria: Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 10 mm in the longest diameter Evaluable disease, defined as lesions on chest CT scan that are not measurable (e.g., ill-defined masses or mediastinal or hilar adenopathy) No metastatic disease except peribronchial/hilar lymph nodes (N1) or ipsilateral/subcarinal mediastinal lymph nodes (N2) No N3 lymph nodes (e.g., contralateral mediastinal/hilar or supraclavicular/scalene) by CT scan or positron emission tomography (PET) scan AND mediastinoscopy No T4 primary tumor (e.g., mediastinal invasion) No malignant pleural effusion Nonmalignant effusions (i.e., negative cytology, non-bloody, and transudate) allowed Effusions visible only by CT scan and not large enough for safe thoracentesis allowed No exudative effusion, defined by 1 of the following criteria: Pleural fluid protein:serum protein ratio > 0.5 Pleural fluid lactic dehydrogenase (LDH):serum LDH ratio ≥ 0.6 Pleural fluid LDH > 200 IU/L No more than 1 area of fludeoxyglucose (FDG) uptake outside the area of the primary lung tumor OR evidence of malignant pleural disease as evidenced by pleural nodules by PET scan Single areas of FDG uptake will be further evaluated (e.g., by biopsy) for metastatic disease PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-1 Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 9 g/dL Hepatic Bilirubin ≤ 1.5 mg/dL SGOT or SGPT ≤ 1.5 times upper limit of normal Renal Creatinine clearance ≥ 45 mL/min Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment No other active malignancy within the past 2 years except nonmelanoma skin cancer or carcinoma in situ of the cervix No psychological, familial, sociological, or geographical situation that would preclude study compliance PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy No prior chemotherapy for lung cancer Endocrine therapy Not specified Radiotherapy No prior radiotherapy for lung cancer Surgery No prior surgery for lung cancer At least 12 weeks since prior major surgery to the chest and abdomen Other No concurrent aspirin or other nonsteroidal anti-inflammatory drugs for ≥ 2 days before (5 days for drugs with a long half-life [e.g., naproxen, piraoxicam, difunisal, nabumetone, rofecoxib, or celecoxib] or 8 days for long acting agents), during, and for 2 days after completion of each pemetrexed disodium administration No concurrent participation in another study involving chemotherapy or radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neoadjuvant chemotherapy<br>Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over approximately 1 hour on day 1. Treatment repeats every 21 days for 3 courses | Drug: cisplatin<br>* Given IV<br>Drug: pemetrexed disodium<br>* Given IV<br>Procedure: adjuvant therapy<br>* Metastasis prevention/control<br>Procedure: conventional surgery<br>* Undergoing tissue removal<br>Procedure: neoadjuvant therapy<br>* Tumor Reduction<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologically Complete Response | Pathologic Complete Response is defined by a surgical pathology specimen, which is free of all gross and microscopic evidence of viable tumor. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events | Frequency of Adverse Events, Graded According to NCI CTCAE v3.0. Please refer to the adverse event reporting for more detail. | 1 year | 
| Overall Survival | Overall survival was defined as time from date of treatment initiation until date of death due to any cause. | Every 6 months until the time of death up to 126 months | 
| Disease Free Survival | Progressive disease is defined as at least a 20% increase in the sum of the longest diameter of target lesions or the appearance of new lesions. Disease Free Survival was defined as time from date of treatment initiation until date of first documented progression or date of death from any cause, whichever came first. | At least every 3 months after the completion of adjuvant therapy for two years and thereafter every 6 months for 3 years and then yearly up to 126 months | 
| Correlation Between Response and Markers Such as Presence or Absence of ERCC1 and DHFR, TS, DPD and GARFT |  | 1 year | 
| Percent Change in SUV Level Between Pre and Post Chemotherapy | Percent change of PET/SUV levels between baseline and post-chemotherapy. | Baseline and post-chemotherapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, stage II non-small cell lung cancer, stage I non-small cell lung cancer