An Alternative Radiation Fractionation Strategy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Study Overview
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Brief Summary
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This phase I trial studies the best dose of radiation therapy in treating patients with locally advanced non-small cell lung cancer that cannot be removed by surgery. Radiation therapy uses high energy x rays to kill tumor cells. Specialized radiation therapy, such as stereotactic body radiation therapy (SBRT), that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. SBRT has been shown to provide excellent results when used in early stage lung cancer, but has not yet been applied to patients with more advanced disease.

Detailed Description
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PRIMARY OBJECTIVE: To test the safety and tolerability of an alternative fractionation regimen in locally advanced non-small cell lung cancer (NSCLC), consisting of 44 Gy with concurrent chemotherapy followed by a stereotactic body radiation therapy (SBRT) boost to remaining parenchymal and nodal disease. The maximum tolerated dose of the SBRT boost will be determined. SECONDARY OBJECTIVES: To assess local control. To assess distant metastasis and patterns of failure. To assess overall survival at 1 and 2 years. OUTLINE: This is a dose-escalation study of radiation therapy and SBRT. Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart. After completion of study treatment, patients are followed up for 5 years.

Official Title
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An Alternative Radiation Fractionation Strategy for Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

Conditions
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Stage IIA Non-small Cell Lung Cancer, Stage IIB Non-small Cell Lung Cancer, Stage IIIA Non-small Cell Lung Cancer, Stage IIIB Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: stereotactic body radiation therapy
* Drug: carboplatin
* Drug: paclitaxel
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven NSCLC, within 8 weeks prior to patient registration Unresectable disease Clinical stage Tx, T1-T4, N1-3, M0 Karnofsky performance status (KPS) ≥ 70 Pretreatment positron emission tomography (PET) CT scan to rule out metastatic disease The primary tumor may not be larger than 8 cm in maximum dimension If the primary tumor is central in location, defined as within 2 cm from the tracheobronchial tree, it must be no larger than 5 cm Mediastinal and hilar lymphadenopathy can be no larger than 5 cm at any nodal station Pretreatment brain CT with contrast or brain MRI to rule out metastases Pathologic assessment of the mediastinum to document involved nodal stations All of the above inclusion criteria must occur within 8 weeks prior to patient registration, with the exception of pathologic assessment of the mediastinum and biopsy to confirm NSCLC, which can be done within 12 weeks of patient registration Exclusion Criteria: Prior history of lung cancer Pregnancy Prior history of radiation to the chest

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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 (radiation therapy, carboplatin, paclitaxel, SBRT)<br>Patients undergo radiation therapy daily and receive carboplatin and paclitaxel weekly for 4.5 weeks. Patients then undergo 2 boost SBRT treatments 2-3 days apart. | Radiation: stereotactic body radiation therapy<br>* Undergo SBRT<br>* Other names: stereotactic radiotherapy;Drug: carboplatin<br> <br> * Other names: Paraplatin;Drug: paclitaxel<br> <br> * Other names: Taxol;Radiation: radiation therapy<br>* Undergo radiation therapy<br>* Other names: therapy, radiation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) defined to be the dose level that results in a probability equal to 0.33 that a dose limiting toxicity (DLT) will be manifest using Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v.4) |  | Up to 1 year | 
| Acute toxicities associated with this regimen using CTCAE v.4 | Crude rates of grade 3 and greater acute toxicities will be reported. | Up to 90 days | 
| Late toxicities associated with this regimen using CTCAE v.4 | Crude rates of grade 3 and greater late toxicities will be reported. | After 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local control | Will be calculated for the entire cohort using Kaplan-Meier methodology. | Up to 5 years | 
| Distant metastasis | Will be calculated for the entire cohort using Kaplan-Meier methodology. | Up to 5 years | 
| Patterns of failure | Will be assessed with standard follow-up imaging, and the percentages of in-field failures versus regional nodal failures calculated. | Up to 5 years | 
| Overall survival | Will be calculated for the entire cohort using Kaplan-Meier methodology. | At 1 year | 
| Overall survival | Will be calculated for the entire cohort using Kaplan-Meier methodology. | At 2 years | 
| Overall survival | Will be calculated for the entire cohort using Kaplan-Meier methodology. | At 5 years |