Carboplatin, Paclitaxel, Selenomethionine, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed by Surgery

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Selenomethionine may slow the growth of tumor cells. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving combination chemotherapy together with selenomethionine and radiation therapy may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well selenomethionine works when given together with carboplatin, paclitaxel, and radiation therapy in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.

Detailed Description
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OBJECTIVES: Primary Determine the safety and tolerability of selenomethionine in combination with chemotherapy and radiotherapy in patients with unresectable stage IIIA or IIIB non-small cell lung cancer. Determine if the incidence of excessive adverse events, in the form of esophagitis, pneumonitis, and myelosuppression, can be reduced with this regimen. Secondary Estimate response rate, failure-free survival, and overall survival of these patients. Correlate selenium levels with degree of observed adverse events. OUTLINE: This is a multicenter study. Patients receive oral selenomethionine twice daily for 1 week and then once daily for 6 weeks. Patients also receive paclitaxel IV over 1 hour once weekly and carboplatin IV over 30 minutes once weekly for 6 weeks and undergo radiotherapy 5 days a week for 6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and weekly during treatment and analyzed by absorption spectrophotometry for selenium measurement of drug concentration After the completion of study treatment, patients are followed periodically.

Official Title
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Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination With Radiation for Patients With Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II, Multi-Center Trial

Conditions
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Lung Cancer

Intervention / Treatment
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* Dietary Supplement: selenomethionine
* Drug: carboplatin
* Drug: paclitaxel
* Other: laboratory biomarker analysis
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC), including any of the following histologic subtypes: Squamous cell carcinoma Adenocarcinoma (including bronchoalveolar cell carcinoma) Large cell anaplastic carcinoma (including giant and clear cell carcinoma) Stage IIIA disease OR selected stage IIIB disease T1-2, N2 disease OR T3, N2 or T4, N0-N2 disease (if based on tumor closeness to the carina, invasion of the mediastinum, or invasion of the chest wall) Contralateral mediastinal disease (N3) allowed if all gross disease can be encompassed in the radiation boost field Tumors adjacent to a vertebral body allowed unless there is demonstrable bone invasion All gross disease must be able to be encompassed in the radiation boost field No direct invasion of a vertebrae body Unresectable or inoperable disease Measurable disease Suitable for radiotherapy, as deemed by the radiation oncologist No scalene, supraclavicular, or contralateral hilar node involvement Pleural effusion allowed provided it is transudate, cytologically negative, and non-bloody, and, according to the radiation oncologist, the tumor can be encompassed within a reasonable radiation field Pleural effusion seen on chest CT scan, but not on chest x-ray, that is too small to tap is allowed No exudative, bloody, or cytologically malignant effusions No known brain metastases PATIENT CHARACTERISTICS: ECOG performance status 0-1 ANC ≥ 1,500/mm³ Platelet count ≥ 75,000/mm³ Total bilirubin ≤ 1.5 mg/dL Creatinine normal Alkaline phosphatase AND AST or ALT meeting 1 of the following criteria: Alkaline phosphatase normal AND AST or ALT ≤ 5 times upper limit of normal (ULN) Alkaline phosphatase ≤ 2.5 times ULN AND AST or ALT ≤ 1.5 times ULN Alkaline phosphatase ≤ 5 times ULN AND AST or ALT normal Able to swallow oral medications No peripheral neuropathy > grade 1 No history of allergic reactions attributed to compounds of similar chemical or biologic composition to selenomethionine or agents formulated with Cremophor EL No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Clinically significant cardiac arrhythmia Psychiatric illness or social situations that would limit compliance with study requirements No currently active second malignancy other than non-melanoma skin cancer Patients are considered not to have an active malignancy if they have completed therapy and are considered by their physician to be at less than 30% risk of relapse Not pregnant Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: At least 2 weeks since prior formal exploratory thoracotomy (N2 node identified making patient ineligible for surgery) No prior chemotherapy or radiotherapy for NSCLC No prior taxanes or platinum drugs No other concurrent investigational agents or anticancer therapy No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent chemotherapy or hormonal therapy, except for the following: Steroids administered for adrenal failure or septic shock Hormones administered for non-disease-related conditions (e.g., insulin for diabetes) Glucocorticosteroids administered as antiemetics

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: CPSR<br>Concurrent Carboplatin, Paclitaxel and Selenomethionine in Combination with Radiation | Dietary Supplement: selenomethionine<br>* Oral Twice daily<br>Drug: carboplatin<br>* Weekly IV<br>Drug: paclitaxel<br>* Weekly IV<br>Other: laboratory biomarker analysis<br>* Correlative Study<br>Radiation: radiation therapy<br>* Undergoing radiation Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Grade 3-4 Esophagitis |  | During study treatment, up to 6 weeks | 
| Incidence of Grade 3-4 Pneumonitis |  | During study treatment, up to 6 weeks | 
| Incidence of Grade 3-4 Myelosuppression |  | During study treatment, up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | 1 month post-treatment, then q 3 months x 4 | 
| Failure-free Survival |  | Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter. | 
| Overall Survival |  | Post-treatment follow-up every 3 months x4, then per institute standard of practice every 6 months for 2 years, then yearly therafter | 
| Selenium Level by Incidence of SAE | Median Selenium level by Incidence of SAE. Mann-Whitney-Wilcoxon test was used to test the correlation between selenium levels and serious adverse events. | Pre-treatment and every week for 6 weeks prior to chemotherapy. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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squamous cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer, large cell lung cancer, stage IIIA non-small cell lung cancer, stage IIIB non-small cell lung cancer, adenosquamous cell lung cancer