Cisplatin, Pemetrexed Disodium, and Radiation Therapy Followed by Docetaxel in Treating Patients With 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 cisplatin, pemetrexed disodium, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving more than one chemotherapy drug (combination chemotherapy) together with radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving cisplatin and pemetrexed disodium together with radiation therapy followed by docetaxel works in treating patients with stage III non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary Assess 1-year survival of stage III non-small cell lung cancer (NSCLC) patients treated with cisplatin, pemetrexed disodium, and concurrent thoracic radiotherapy followed by consolidation therapy with docetaxel. Secondary Assess the progression-free survival and overall survival. Assess the toxicity of this regimen. OUTLINE: Patients receive pemetrexed disodium IV over 10 minutes followed by cisplatin IV over 60 minute on day 1. Treatment repeats every 21 days for 3 courses in the absence of unacceptable toxicity. Patients also receive concurrent thoracic radiotherapy in weeks 1-7. Between 3-8 weeks after completion of chemoradiotherapy, patients with no progressive disease receive docetaxel IV over 1 hour on day 1. Treatment with docetaxel repeats every 21 days for 3 courses. After completion of study therapy, patients are followed at 1 month and periodically thereafter. PROJECTED ACCRUAL: A total of 28 patients will be accrued for this study.

Official Title
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Phase II Study of Concurrent Cisplatin/Pemetrexed and RT Followed by Docetaxel in Stage III NSCLC (Non Small Cell Lung Cancer)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Cisplatin
* Drug: Docetaxel
* Drug: Pemetrexed disodium
* Radiation: Radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologic or cytologic diagnosis of non-small cell lung cancer (NSCLC), meeting 1 of the following staging criteria: Stage IIIA disease, meeting all of the following criteria: Mediastinal lymph node involvement Greater than one mediastinal lymph node enlarged on CT scan, confirmed by positron emission tomography (PET) scan Paralyzed left vocal cord with separate lung primary distinct from the aorto-pulmonary lymph nodes on the CT scan Stage IIIB disease, meeting all of the following criteria: N3 lymph node involvement Enlarged N3 lymph nodes on CT scan confirmed by PET scan Lymph node involvement may not extend to cervical lymph nodes other than supraclavicular lymph nodes Right-sided primary tumor with left vocal cord paralysis Evidence of tumor extension into the mediastinum and/or mediastinal structures by mediastinoscopy, bronchoscopy, or CT scan No evidence of malignant pleural effusion unless effusion is only evident on CT scan No more than 1 parenchymal lesions on the same or opposite sides of the lung No brain metastases by CT scan or MRI PATIENT CHARACTERISTICS: SWOG performance status 0 or 1 Platelet count ≥ 100,000/mm³ Absolute neutrophil count ≥ 1,500/mm³ Creatinine ≤ 1.5 times upper limit of normal (ULN) Creatinine clearance ≥ 45 mL/min Bilirubin normal Transaminases (SGOT and/or SGPT) ≤ 1.5 times ULN Alkaline phosphatase ≤ 2.5 times ULN Total lung volume (i.e., right and left lung minus the gross tumor volume) receiving greater than 20 Gy of radiation ≤ 40% FEV_1 ≥ 70% of predicted DLCO ≥ 50 mL/min No other concurrent malignancy Prior malignancy allowed provided it is in clinical control and is not likely to impact clinical outcome in the opinion of the treating physician No peripheral neuropathy ≥ grade 2 No serious medical illness, including, but not limited to, any of the following: Uncontrolled congestive heart failure Uncontrolled angina Myocardial infarction Cerebrovascular event within the past 6 months History of chronic active hepatitis History of HIV infection Active bacterial infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Must be willing and able to take folic acid, cyanocobalamin (vitamin B12), or dexamethasone PRIOR CONCURRENT THERAPY: No prior chemotherapy or radiotherapy for NSCLC No concurrent participation in another therapeutic investigational study Concurrent ibuprofen (400 mg four times daily) allowed during pemetrexed disodium administration provided the patient has normal renal function No concurrent aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) 2 days before, during, and for 2 days after pemetrexed disodium administration Patients on long-acting NSAIDs (e.g. naproxen sodium, diflunisal, nabumetone, or celecoxib) must be willing or able to discontinue usage 5 days prior to, during, and for 2 days after pemetrexed disodium administration

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: Cisplatin, Docetaxel & Radiation Therapy<br>Cisplatin 75 mg/m2 every 3 weeks on days 1, 22, and 43; Docetaxel 75 mg/m2 on day 1 of each cycle; Radiation therapy will begin within 24 hours of the first cycle of chemotherapy. | Drug: Cisplatin<br>* Cisplatin 75 mg/m2 every 3 weeks on days 1, 22, and 43<br>* Other names: Cisplatinum;Drug: Docetaxel<br>* Docetaxel 75 mg/m2 on day 1 of each cycle<br>* Other names: Taxotere®;Drug: Pemetrexed disodium<br>* Pemetrexed 500 mg/m2 every 3 weeks on days 1, 22, and 43<br>* Other names: Alimta;Radiation: Radiation therapy<br>* Radiation therapy will begin within 24 hours of the first cycle of chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of Overall Survival at One Year | Overall Survival at one year using Kaplan-Meier product-limit analysis | at 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival using Kaplan-Meier estimates | Approximately 3 weeks after the last cycle of cisplatin/pemetrexed or completion of radiation whichever is the later. | 
| Overall Survival | Overall survival using Kaplan-Meier estimates | Date of registration to the date of death | 
| Safety Outcomes | Toxicity: total number of SAEs and other AEs | 72 hours after 2nd and 3rd cycles: 30 days after completion of study treatment; Every 2 months thereafter; then once a year | 

 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