Accelerated Hypofractionated Radiation Therapy Immediately Before Surgery in Treating Patients With Malignant Pleural Mesothelioma

Study Overview
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Brief Summary
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This pilot phase 0 trial studies accelerated hypofractionated radiation therapy immediately before surgery in treating patients with malignant pleural mesothelioma (cancer in the thin layer of tissue that covers the lungs and lines the interior wall of the chest cavity). Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Hypofractionated radiation therapy is a type of radiation therapy in which the total prescribed dose of radiation is divided into fewer but larger doses as compared to conventional radiation therapy. Giving accelerated hypofractionated radiation therapy immediately before surgery may improve survival, and may also reduce side effects experienced by patients with pleural mesothelioma.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the feasibility and toxicity (both acute and chronic) of accelerated hypofractionated neoadjuvant helical intensity modulated radiation therapy prior to pleurectomy/decortication for malignant pleural mesothelioma. SECONDARY OBJECTIVES: I. To determine the pathologic complete response rate (pCR). II. To determine the tumor local control rate (LC). III. To determine the malignant pleural mesothelioma disease specific survival (DSS). IV. To determine the overall survival (OS). V. To assess transforming growth factor beta (TGF-B), interleukin (IL)-1, and IL-6 levels as predictive biomarkers for treatment induced tissue injury. VI. To assess the changes in the postoperative pleural immunological milieu in terms of chemo- and cytokine expression. OUTLINE: Patients undergo 5 fractions of accelerated hypofractionated intensity-modulated radiation therapy (IMRT) over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. After completion of study treatment, patients are followed up at 6 weeks, and then every 3 months for 5 years.

Official Title
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Neoadjuvant Accelerated Hypofractionated Radiation Therapy Immediately Prior to Radical Pleurectomy/Decortication for Malignant Pleural Mesothelioma: A Pilot Study

Conditions
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Pleural Epithelioid Mesothelioma, Pleural Malignant Mesothelioma

Intervention / Treatment
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* Radiation: Hypofractionated Radiation Therapy
* Radiation: Intensity-Modulated Radiation Therapy
* Other: Laboratory Biomarker Analysis
* Procedure: Therapeutic Conventional Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed epithelioid predominantly (> 70%) subtype malignant pleural mesothelioma Patient must have been evaluated by a University of California Los Angeles (UCLA) thoracic surgeon, and deemed medically and technically suitable for a pleurectomy/decortication procedure Karnofsky performance status (KPS) >= 70 or Eastern Cooperative Oncology Group (ECOG) 0-2 If a woman is of childbearing potential, a negative urine or serum pregnancy test must be documented; women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for duration of study participation and for up to 4 weeks following the study Exclusion Criteria: Patients who have previously received therapeutic radiation therapy to the chest Active systemic, pulmonary, or pericardial infection Use of chemotherapy within 4 weeks of the planned start of radiation therapy Pregnant women, or women of childbearing potential who are sexually active and not willing/able to use medically acceptable forms of contraception for the entire study period and for up to 4 weeks after the study Refusal to sign the informed consent Patients who are participating in a concurrent treatment protocol

Ages Eligible for Study
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Minimum Age: 18 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: Treatment (hypofractionated IMRT, pleurectomy/decortication)<br>Patients undergo 5 fractions of accelerated hypofractionated IMRT over 1 week with simultaneous integrated boost to gross disease. Patients then undergo pleurectomy/decortication within 14 days after completion of IMRT. | Radiation: Hypofractionated Radiation Therapy<br>* Undergo accelerated hypofractionated IMRT<br>* Other names: hypofractionation;Radiation: Intensity-Modulated Radiation Therapy<br>* Undergo accelerated hypofractionated IMRT<br>* Other names: Intensity-Modulated Radiotherapy;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Procedure: Therapeutic Conventional Surgery<br>* Undergo pleurectomy/decortication<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to Accrue Sufficient Patients to Draw Conclusions About Endpoints in a Timely and Expedient Manner | No data displayed because Outcome Measure has zero total participants analyzed. | Up to 1 year | 
| Incidence of Acute and Subacute Toxicity Defined as Grade 4 or 5 Adverse Events as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | No data displayed because Outcome Measure has zero total participants analyzed. | Up to 3 months | 
| Incidence of Chronic Toxicity as Assessed by the NCI CTCAE Version 4.0 | No data displayed because Outcome Measure has zero total participants analyzed. | Up to 5 years post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Specific Survival (DSS) | Cumulative incidence approach will be used to estimate DSS. No data displayed because Outcome Measure has zero total participants analyzed. | Up to 5 years post-treatment | 
| Local Control (LC) | Cumulative incidence approach will be used to estimate the local failure rates. No data displayed because Outcome Measure has zero total participants analyzed. | Up to 5 years post-treatment | 
| Overall Survival (OS) | No data displayed because Outcome Measure has zero total participants analyzed. | Up to 5 years post-treatment | 
| Pathologic Complete Response Rate (pCR) | No data displayed because Outcome Measure has zero total participants analyzed. | Up to 5 years post-treatment |