Esophageal Sparing Intensity-modulated Radiation Therapy (IMRT) for Locally-Advanced Thoracic Malignancies

Study Overview
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Brief Summary
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Hypothesis 1- Using IMRT, the radiation therapy (RT) dose can be safely escalated from 58 Gy to 74 Gy given as 6 fractions/week with concurrent chemotherapy. Hypothesis 2- Esophageal motion can be used to customize planning organ at risk volumes. Hypothesis 3- Biological predictors of acute esophagitis can be used to identify patients at high risk of developing esophageal toxicity from radiation therapy and chemotherapy.

Detailed Description
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Prospective phase I study designed to determine the maximum tolerated dose of radiation therapy given in an accelerated fashion (2 Gy/fraction, 6 fractions/week) with concurrent chemotherapy. Intensity-modulated radiation therapy (IMRT) will be utilized to spare the esophagus. All patients on the dose escalation study will participate in additional assessments evaluating esophageal motion and esophageal toxicity from radiation therapy.

Official Title
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Phase I Dose Escalation Study of Accelerated Fractionation With Esophageal Sparing Using Intensity-Modulated Radiation Therapy for Locally-Advanced Thoracic Malignancies Including a Prospective Assessment of Esophageal Motion and Radiation-Induced Esophageal Injury

Conditions
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Non Small Cell Lung Cancer, Small Cell Lung Cancer, Thymoma, Thymus Neoplasms

Intervention / Treatment
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* Radiation: Esophageal sparing IMRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic documentation of one of the following thoracic malignancies: Non-small cell lung cancer (stage III or X (recurrent) with disease confined to local/regional sites) Small cell lung cancer (stage II-III) Thymoma (unresectable) Thymic carcinoma (unresectable) Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Weight loss < 10% in preceding 3 months prior to diagnosis ANC > or = 1500 and platelet count > or = 100,000. Creatinine clearance greater than 50 ml/min 18 years of age or older. Negative pregnancy test in women of child-bearing potential Exclusion Criteria: Prior thoracic irradiation Medical contraindications to thoracic irradiation

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: IMRT concurrent with chemotherapy<br>6 fractions of esophageal sparing IMRT weekly for 5-6 weeks (dependent on dose cohort) concurrent with standard chemotherapy: Cisplatin 50 mg/m2 /d intravenously (IV) on days 1, 8, 29, and 36. Etoposide 50 mg/m2 /d IV on days 1 through 5 and 29 through 33. | Radiation: Esophageal sparing IMRT<br>* 6 fractions/week of 2Gy each for 29 fx (58 Gy), 31 fx (62 Gy), 33 fx (66 Gy), 35 fx (70 Gy), or 37 fx (74 Gy).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) of IMRT |  | within 30 days of completing RT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The occurrence of RT-induced acute esophagitis |  | One year | 
| To determine if biological predictors of esophagitis can identify patients who develop severe esophageal toxicity during radiation therapy | Blood will be drawn at specific time intervals, plasma will be analysed for Glutathione Oxidation, Citrulline, Lipid peroxidation, DNA oxidation, and Tetrahydrobiopterin. | Two 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, Small cell lung cancer, Thymoma unresectable, Thymic carcinoma unresectable