Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body RadioTherapy and REsection

Study Overview
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Brief Summary
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Despite improved staging and operative techniques, the rate of incomplete resection (R1) of NSCLC has remained significant over the last decades. Patients with R1 resection have significantly worse survival compared to those with complete resection (R0). This is a phase I study that investigates the feasibility and safety of delivering Stereotactic Body Radiotherapy (SBRT) to patients with locally invasive NSCLC (cT3-4, N0-1) who are at risk for incomplete resection. Twenty patients with NSCLC will be treated with SBRT followed by surgery and appropriate adjuvant therapy. Patients will be divided into groups, of 5 patients each, treated with escalating doses (35, 40, 45 and 50 Gy) in 10 daily fractions. The primary outcome is the feasibility i.e. the ability to complete safely SBRT and surgery (within 6 weeks). Secondary outcomes include acute and late adverse events, R0/R1/R2 rates and secondary surrogates of feasibility. If successful, this study will lead to further evaluation of pre-operative SBRT in NSCLC.

Official Title
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Phase I Study: Locally Invasive NSCLC Treated With NEo-Adjuvant Stereotactic Body Radiotherapy and REsection

Conditions
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Non-Small-Cell Lung Cancer, Carcinoma

Intervention / Treatment
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* Radiation: Neoadjuvant Stereotactic body radiation (SBRT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients will be included if they are aged 18 years or older, with biopsy proven NSCLC, clinically staged T3-T4 marginally resectable i.e. deemed at risk to achieve <R0 resection (such as invasion of critical mediastinal or hilar structures, nodal extra-capsular extension, chest wall, vertebral bodies, compromised bronchial stump margin, based on CT images of the chest). Patients also need to be pathologically staged N0-1 disease, with an SBRT CTV≤200cm3, based on planning CT images. ECOG status is required to be <2 within 4 weeks prior to registration and patients must be deemed medically operable by the surgical team. Exclusion Criteria: Patients will be excluded if they are deemed medically inoperable by the surgical team and have a weight loss of ≥10% within 3 months prior to pathological diagnosis. Patients will also have no absolute contraindication to RT such as connective tissue disease, pacemaker-dependent patient with the pacemaker receiving higher than tolerance dose, had no had previous RT to the current region of the study, that would result in overlap of RT fields, patients must have no plans to receive other local therapy while on study, except at disease progression, patients have not had other malignancy within 2 years prior to the study (other than non-melanomatous skin cancers)

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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Accepts Healthy Volunteers

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: Neoadjuvant stereotactic body radiation<br>Single arm study. Four cohorts of 5 patients will undergo neo-adjuvant SBRT for lung cancer. Eligible patients will have operable, borderline resectable lung cancer , they will be treated with SBRT, prior to undergoing surgical resection. | Radiation: Neoadjuvant Stereotactic body radiation (SBRT)<br>* Dose escalation of neo-adjuvant SBRT in operable patients with locally advanced non-small cell lung cancer. The first cohort will be treated with a dose of 35 Gy in 10 fractions, the second cohort will be treated with a dose of 40 Gy in 10 fractions, the third cohort will be treated with a dose of 45 Gy in 10 fractions, the fourth cohort will be treated with a dose of 50 Gy in 10 fractions. The SBRT doses will be escalated only once all patients in the previous cohort will have completed safely their treatments.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of SBRT followed by surgery (proportion of patients who can undergo 10 fractions of SBRT followed by Surgery) | Feasibility of neo-adjuvant SBRT followed by surgery. This will be measured as the proportion of patients who can undergo 10 fractions of SBRT followed by Surgery as scheduled (within 6 weeks from registration). | 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Early safety of SBRT-S through collection of serious adverse events (CTCAE version 4.0 grade 3 or higher) from beginning of SBRT to 4 weeks after completion of surgery. |  | 18 months | 
| Late safety profile of SBRT-S through collection of surgical complication rates assessed at 6 and 18 months post-registration (thus 30 months from opening of the study, assuming it takes 1 year to complete accrual). | Complications recorded include incidence of bronchopleural fistula, esophageal fistula, wound healing complications (dehiscence, infection) and post-operative pulmonary complications). | 30 months | 
| Secondary feasibility outcomes (including accrual rate, consent rate, rates of deviation from scheduled treatment plan, and reasons for delay) | These include accrual rate, consent rate, rates of deviation from scheduled treatment plan of 6 weeks, and reasons for delay) | 18 months | 
| Pathological response following neoadjuvant SBRT (proportion of R0, R1 and R2 resections) | To determine the proportion of R0, R1 and R2 resections after neoadjuvant SBRT. | 18 months | 
| Pathologic changes associated with neo-adjuvant SBRT with analysis of irradiated tissues |  | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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radiosurgery, Neoadjuvant Therapy