Stereotactic Body Radiation Therapy Followed by Surgery in Treating Patients With Stage I-IIIA Non-small Cell Lung Cancer

Study Overview
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Brief Summary
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This pilot clinical trial studies the effects of stereotactic body radiation therapy followed by surgery in treating patients with stage I-IIIA non-small cell lung cancer. Stereotactic body radiation therapy is a method of radiation that uses imaging to precisely locate a tumor and then deliver very high radiation doses to the tumor site in order to limit normal tissue toxicity or damage.

Detailed Description
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PRIMARY OBJECTIVES: I. To assess the safety and feasibility of combining single fraction stereotactic body radiation therapy (SBRT) followed by surgery, in thoracic malignancies. SECONDARY OBJECTIVES: I. To estimate overall survival (OS) and progression-free survival (PFS) after single fraction SBRT followed by surgery, in thoracic malignancies. II. To define any differences in quality of life/toxicity following SBRT based on tumor location/stage/tumor type. TERTIARY OBJECTIVES: I. To assess changes in T cell mediated immunity following SBRT in thoracic malignancies. OUTLINE: Patients are assigned to 1 of 3 studies. STUDY 1: Patients with stage I or II non-small cell lung cancer (NSCLC) in the peripheral lung undergo highest-dose of SBRT over a single treatment fraction on day 1. Patients then undergo thoracic surgery on day 28. STUDY 2: Patients with stage I or II NSCLC in the central lung undergo lowest-dose of SBRT over a single treatment fraction on day 1. Patients then undergo thoracic surgery on day 28. STUDY 3: Patients with stage IIIA NSCLC in the any lung location undergo lowest- or higher-dose of SBRT over a single treatment fraction on day 1. Patients then undergo thoracic surgery on day 28. After completion of study treatment, patients are followed up at 6, 9, and 12 months, every 6 months for 2 years, and then annually for 2 years.

Official Title
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Three Pilot Studies of Stereotactic Body Radiation Therapy (SBRT) and Surgery in Non-small Cell Lung Cancer

Conditions
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Stage I Non-Small Cell Lung Cancer AJCC v7, Stage IA Non-Small Cell Lung Carcinoma AJCC v7, Stage IB Non-Small Cell Lung Carcinoma AJCC v7, Stage II Non-Small Cell Lung Cancer AJCC v7, Stage IIA Non-Small Cell Lung Carcinoma AJCC v7, Stage IIB Non-Small Cell Lung Carcinoma AJCC v7, Stage IIIA Non-Small Cell Lung Cancer AJCC v7

Intervention / Treatment
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* Other: Laboratory Biomarker Analysis
* Other: Quality-of-Life Assessment
* Drug: Stereotactic Body Radiation Therapy
* Drug: Stereotactic Body Radiation Therapy
* Drug: Stereotactic Body Radiation Therapy
* Procedure: Thoracic Surgical Procedure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have an Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 Have histologically proven diagnosis of: non-small cell lung cancer (NSCLC) (stage I, II, or IIIa) Neoadjuvant or induction chemotherapy or biological (immune, vaccine, etc.)therapy for stage IIIa is allowed Chemotherapy for another invasive malignancy is permitted if it has been treated definitively and the patient has remained disease free for >3 years Participant is able to undergo surgery (planned lobectomy or wedge resection) Specifically, the participant has been or will have been cleared for surgery at the time of enrollment; the surgeon can accept the baseline tests done within 45 days prior to SBRT to clear the patient for surgery Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g., hormonal or barrier method of birth control; abstinence) during treatment Participant or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Contraindication to SBRT (this includes the inability to cooperate with any aspect of SBRT: such as the inability to lie still and breathe reproducibly) Previous radiotherapy to the volume of lung or mediastinum currently involved by tumor Previous surgery for this lung or mediastinum tumor Plans for the patient to receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery) while on this protocol(does not apply to neoadjuvant therapy as in inclusion criteria) except at disease progression Patients with active systemic, pulmonary, or pericardial infection Pregnant or nursing female participants Unwilling or unable to follow protocol requirements Any condition which in the investigator?s opinion deems the participant ineligible Received an investigational agent within 30 days prior to enrollment Stage IIIb

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study 1 (highest-dose of SBRT, surgery)<br>Patients with stage I or II NSCLC in the peripheral lung undergo highest-dose of Stereotactic Body Radiation Therapy over a single treatment fraction on day 1. Patients then undergo thoracic surgery on day 28. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Drug: Stereotactic Body Radiation Therapy<br>* Undergo highest-dose of SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;Procedure: Thoracic Surgical Procedure<br>* Undergo thoracic surgery<br>* Other names: Thoracic Surgical Procedures;|
| Experimental: Study 2 (lowest-dose of SBRT, surgery)<br>Patients with stage I or II NSCLC in the central lung undergo lowest-dose of Stereotactic Body Radiation Therapy over a single treatment fraction on day 1. Patients then undergo thoracic surgery on day 28. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Drug: Stereotactic Body Radiation Therapy<br>* Undergo lowest-dose of SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;Procedure: Thoracic Surgical Procedure<br>* Undergo thoracic surgery<br>* Other names: Thoracic Surgical Procedures;|
| Experimental: Study 3 (lowest- or higher-dose of SBRT, surgery)<br>Patients with stage IIIA NSCLC in the any lung location undergo lowest- or higher-dose of Stereotactic Body Radiation Therapy over a single treatment fraction on day 1. Patients then undergo thoracic surgery on day 28. | Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Drug: Stereotactic Body Radiation Therapy<br>* Undergo lowest- or higher-dose of SBRT<br>* Other names: Stereotactic Ablative Body Radiation Therapy;Procedure: Thoracic Surgical Procedure<br>* Undergo thoracic surgery<br>* Other names: Thoracic Surgical Procedures;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-related grade 3-5 adverse events assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0 | Comparison will be made with published historical and contemporaneous rates of toxicity with standard of care therapy for each of the study groups. | Up to 10 weeks post-surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Will be measured and compared with published historical and contemporaneous rates of toxicity with standard of care therapy for each of the study groups. | Up to 5 years | 
| Progression free survival | Will be measured and compared with published historical and contemporaneous rates of toxicity with standard of care therapy for each of the study groups. | Up to 5 years |