Concurrent Proton and Chemotherapy in Locally Advanced Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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The goal of this clinical research study is to learn if proton radiotherapy given with standard chemotherapy (such as paclitaxel and carboplatin) can help to control locally advanced NSCLC. The safety of this treatment will also be studied.

Detailed Description
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A proton beam is made up of charged particles that have a well-defined range of penetration into tissues. How deep it can penetrate is decided by both the beam's energy and the density of the tissue through which it passes. As the proton beam penetrates the body, the particles slow down, and the beam deposits its dose sharply near the end of its range. This is a phenomenon known as the Bragg peak. By adjusting the Bragg peak, the doctor can deliver a full, localized, uniform dose of energy to the treatment site while sparing the surrounding normal tissues. The proton beam is ideal for treatments where organ preservation is very important, such as lung cancer. If you are found to be eligible to take part in this study, you will receive 37 treatments of proton radiotherapy (Monday through Friday for 7 1/2 weeks). During the treatment, you will lie still on a table for about 30-45 minutes per day in the same position. The proton machine will deliver the dose according to the plan designed by the physician and controlled by a computer. You will not feel, see, or smell anything during the proton beam delivery. While on study, you will also be receiving weekly standard low-dose chemotherapy possibly followed by full-dose chemotherapy. During the treatment, you will be seen by a doctor and research nurse once a week to evaluate possible side effects. You will have a physical exam and you will have a medical history. About 2 teaspoons of blood will be drawn for routine tests. You will be taken off study early if the disease gets worse or intolerable side effects occur. After finishing the treatment, 6 week follow up is recommended after completion of radiotherapy, then required every 3 months (+1 month) for 2 years, then every 6 months (+1 month) for 3 years, and then once a year for 2 years. You will have imaging tests (chest CT or positron emission computed tomography (PET) scan) and routine blood tests (about 2 teaspoons) at the follow-up visits. This is an investigational study. Proton radiotherapy is FDA approved for the treatment of lung cancer. A total of 65 patients will be take part in this study. All will be enrolled at MD Anderson.

Official Title
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Phase II Concurrent Proton and Chemotherapy in Locally Advanced Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Lung Cancer

Intervention / Treatment
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* Drug: Carboplatin
* Radiation: Proton Radiotherapy
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented NSCLC. Inoperable stage IIIA (T1--3N2MO, T3N1MO) and IIIB (T1-3N3MO, T4NO-3MO) disease excluding malignant pleural effusion. Performance score Karnofsky Performance Status (KPS) 70-100, Weight loss: less or equal to 10% in 6 months prior to diagnosis. Patient consented for the protocol Induction chemotherapy is allowed. Exclusion Criteria: Prior chest radiotherapy. Previous or concomitant malignancy other than (a) curatively treated carcinoma in situ of cervix, (b) basal cell carcinoma of the skin, (c) curatively treated superficial transitional cell carcinoma of the urinary bladder, and (d) early stage tumor treated more than 3 years ago for cure. Pregnancy. Patients (men and women) of child bearing potential should use an effective (for them) method of birth control throughout their participation in this study. Off study criteria: a) If a patient is found to have distant metastasis during treatment and/or immediate after the treatment (<60 days) indicating inaccurate cancer stage, he or she will be taken off study. b) If a patient does not follow up at MD Anderson and does not forward his or her medical records such as CT, PET/CT, pulmonary function test (PFT) or pathology report as required by protocol, he or she will be taken off study. c) If a patient does not have any required post-treatment evaluation such as images, he or she will be taken off study.
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: Concurrent proton and Chemotherapy<br>Proton Radiotherapy + Carboplatin + Paclitaxel | Drug: Carboplatin<br>* 2 area under curve (AUC) by vein Weekly<br>* Other names: paraplatin;Radiation: Proton Radiotherapy<br>* 2 GY/fraction for 37 fractions (daily treatment, Monday to Friday, for 7.5 weeks).<br>Drug: Paclitaxel<br>* 50 mg/m^2 by vein Weekly<br>* Other names: Taxol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival and Progression Free Survival | The primary objective was to improve overall survival (OS). Patients are recommended to have follow up 6 weeks after completion of concurrent chemo radiotherapy for the evaluation of acute treatment toxicities, then required every 3 months (+ 1 month) for two years, then every 6 months (+ 1 month) for three years and then annually for the rest of their lives, that is standard of care. Statistics were performed with Strata/MP 14.2 software. OS was calculated by Kaplan-Meier Methodology (K-M) from the beginning of enrollment to date of death or last follow-up. Progression-free survival (PFS) was defined from enrollment to any treatment failure or death. PFS will be evaluated by series CT of chest with contrast for every follow up except 6 weeks after the concurrent chemo radiotherapy for two years. Multivariate Cox proportional hazards modeling was used to examine predictors of OS when adjusting for each of the collected potential confounding variables. | The Overall survival (OS): From date of registration to the last follow-up (f/u), or lost to f/u, or death up to 5 years. The progression free survival (PFS): From date of registration to the date of first documented progression or death up to 5 years. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, Lung Cancer, Proton Radiotherapy, Proton Beam, Paclitaxel, Taxol, Carboplatin, Paraplatin, NSCLC