Radical Resection Vs. Ablative Stereotactic Radiotherapy in Patients With Operable Stage I NSCLC

Study Overview
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Brief Summary
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Rationale: Surgery remains the standard of care for stage 1 (T1-2a N0)non-small cell lung cancer. Stereotactic body radiation therapy is a newer radiation treatment that gives fewer but higher and possibly more effective doses of radiation than standard radiation. This technique may be able to send x-rays directly to the tumor and cause less damage to normal tissue. It is not yet known whether stereotactic body radiation therapy is more effective than surgery in treating non-small cell lung cancer. Purpose: The primary aim of this randomized phase II trial is to determine if the efficacy of SBRT is comparable to that of standard surgical interventions for patients with T1N0 non-small cell lung cancer.

Official Title
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POSTILV: A RANDOMIZED PHASE II TRIAL IN PATIENTS WITH OPERABLE STAGE I NON-SMALL CELL LUNG CANCER: RADICAL RESECTION VERSUS ABLATIVE STEREOTACTIC RADIOTHERAPY - This is a Limited Participation Study.

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Radiation: Stereotactic Body Radiation Therapy (SBRT)
* Procedure: Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Pathologically (histologically or cytologically) proven diagnosis of Stage I NSCLC (AJCC, 7th ed.), T1N0M0; note: T1N0 disease must be confirmed by FDG-PET/CT The following primary cancer types are eligible: squamous cell carcinoma; adenocarcinoma; large cell carcinoma/ large cell neuroendocrine carcinoma; non-small cell carcinoma not otherwise specified. Patients with hilar or mediastinal lymph nodes ≤ 1 cm and no abnormal hilar or mediastinal uptake on PET and CT will be considered N0. Mediastinal lymph node biopsy is required for patients with visible nodes: patients with > 1 cm hilar or mediastinal lymph nodes on CT or with nodes appearing as abnormal on PET (including suspicious but nondiagnostic uptake). Such patients will not be eligible unless directed biopsies of all abnormal lymph nodes are negative for cancer or these nodes demonstrate a lack of change during the prior 6 months and thus are considered to be non-malignant. The patient must be considered a reasonable candidate for surgical resection using a lobectomy or pneumonectomy of the primary tumor within 6 weeks prior to registration, according to the following criteria based on the American College of Chest Physicians guidelines [165]: A qualified thoracic surgeon should make the determination that there would be a high likelihood of negative surgical margins; Baseline FEV1 >60% predicted, postoperative predicted FEV1 >40% predicted; Diffusion capacity of the lung for carbon monoxide (DLCO) >60% predicted, postoperative predicted DLCO > 40 % predicted; No baseline hypoxemia and/or hypercapnia; If the estimated postoperative FEV1 or DLCO <40% predicted indicates an increased risk for perioperative complications, including death, from a standard lung cancer resection (lobectomy or greater removal of lung tissue), then cardiopulmonary exercise testing to measure maximal oxygen consumption (VO2max) must be >60%; No severe pulmonary hypertension; No severe cerebral, acute or chronic cardiac, or peripheral vascular disease; Pleural effusion, if present, must be deemed too small to tap under CT guidance and must not be evident on chest x-ray. Pleural effusion that appears on chest x-ray will be permitted only if there is no evidence of malignancy after invasive cytologic assessment. Appropriate stage for protocol entry, including no distant metastases, based upon the following minimum diagnostic workup: History/physical examination, including documentation of weight within 6 weeks prior to registration;; Evaluation by an experienced thoracic surgeon within 6 weeks prior to registration; FDG-PET/CT scan for staging and RT plan within 4 weeks prior to registration; CT scan (preferably with intravenous contrast, unless medically contraindicated) within 4 weeks prior to registration to include the entirety of both lungs, the mediastinum, liver, and adrenal glands; primary tumor dimension will be measured on CT scan. Zubrod Performance Status 0-1 within 6 weeks prior to registration; Age ≥ 18; For women of childbearing potential, a serum or urine pregnancy test must be negative within 72 hours prior to registration; Women of childbearing potential and male participants who are sexually active must practice adequate contraception during treatment if assigned to treatment with SBRT. Patients must provide study specific informed consent prior to study entry. Exclusion Criteria: Direct evidence of regional or distant metastases after PET and surgical staging studies, or synchronous primary malignancy or prior invasive malignancy in the past 3 years, with the following exceptions: carcinoma in situ; early stage skin cancer that has been definitively treated; when an invasive malignancy has been treated definitively and the patient has remained disease free for ≥ 3 years; Primary tumors >3 cm; Prior systemic chemotherapy or thoracic surgery involving lobectomy or pneumonectomy; Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields; Pure bronchioloalveolar carcinoma subtype of non-small cell lung cancer; Active systemic, pulmonary, or pleural pericardial infection; Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Surgery<br>Complete resection, i.e., removal of the primary tumor with at least a 2 cm margin together with nodal dissection/sampling | Procedure: Surgery<br>* Complete resection, i.e., removal of the primary tumor with at least a 2 cm margin together with nodal dissection/sampling<br>* Other names: R0 resection with nodal dissection/sampling (RODS);|
| Experimental: Stereotactic Body Radiation Therapy (SBRT)<br>Stereotactic Body Radiation Therapy (SBRT) given every other day 11 Gy in 5 fractions to a total dose of 55 Gy in 10-15 days with an inter-fraction interval of 2-3 days | Radiation: Stereotactic Body Radiation Therapy (SBRT)<br>* SBRT given every other day 11 Gy in 5 fractions to a total dose of 55 Gy in 10-15 days with an inter-fraction interval of 2-3 days<br>* Other names: Stereotactic Body Radiation Therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local-regional control | The time from randomization until local or regional progression. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Time from randomization until death | 2 years | 
| Disease-free survival | Time from randomization until progression or death, whichever occurs first | 2 years | 
| Frequency of site-specific failure | Local-regional tumor failure; distant metastases; second primary | 2 years | 
| Time to local-regional tumor failure and distant metastases | Time from randomization until local or regional progression, or distant metastases | 2 years | 
| PET tumor response | Assessment of failure patterns after treatment and PET data | 2 years | 
| Frequency of adverse events | Distributions of specific adverse events of interest | 2 years | 
| Trial feasibility parameters | Descriptive statistics relating to rates of credentialing, eligibility, and timely submission of baseline and follow-up forms | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lung Cancer