Radiation Therapy or Observation After Chemotherapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Sometimes, after chemotherapy, the tumor may not need more treatment until it progresses. In this case, observation may be sufficient. It is not yet known whether radiation therapy is more effective than observation after chemotherapy in treating non-small cell lung cancer. PURPOSE: This randomized phase II trial is studying how well radiation therapy works compared with observation after chemotherapy in treating patients with stage IV non-small cell lung cancer.

Detailed Description
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OBJECTIVES: Primary To assess whether the addition of radiotherapy to radiographically apparent residual disease after an initial course of standard chemotherapy results in an improvement in overall survival of patients with oligometastatic stage IV non-small cell lung cancer. Secondary To compare the progression-free survival of patients treated with radiotherapy vs observation after standard chemotherapy. To compare the time to disease progression and time to treatment failure in these patients. To compare the confirmed response rate in these patients. To compare the duration of response in these patients. To compare the adverse events in these patients. OUTLINE: This is a multicenter study. Patients are stratified according to prior treatment with bevacizumab during first-line chemotherapy (yes vs no), number of standard chemotherapy courses (2-3 vs 4-6), Linear Analog Self Assessment value (≤ 7 vs > 7), and histology (predominantly squamous cell vs not predominantly squamous cell). Patients are randomized to 1 of 2 treatment arms. Arm I: Patients undergo observation for 6 weeks. Arm II: Patients undergo radiotherapy 5 days a week for 6 weeks to all sites of gross disease. After completion of study therapy, patients are followed every 3-6 months for up to 5 years.

Official Title
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A Randomized Phase II Study of Oligometastatic Stage IV Non-Small Cell Lung Cancer (NSCLC) Treated With Systemic Therapy Plus Either Radiotherapy to All Sites of Gross Residual Disease or No Radiotherapy

Conditions
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Lung Cancer

Intervention / Treatment
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* Other: clinical observation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) Mixed histology allowed if all components are consistent with NSCLC Squamous cell histology allowed Stage IV disease Oligometastatic disease (M1 with 1-3 metastases) Patients with M1 disease that involves intrapulmonary metastases are eligible provided ≤ 40% of the total lung volume receives ≥ 20 Gy of radiotherapy Previously untreated disease OR achieved stable disease or partial response within 8 weeks after completion of 2-6 courses of standard platinum-based chemotherapy (administered every 3-4 weeks) Pleural effusion allowed provided it is minimal No history of or current brain metastases Patients who have had up to 3 brain metastases allowed provided they have been treated with not signs of progression PATIENT CHARACTERISTICS: ECOG performance status 0-1 Life expectancy ≥ 12 weeks Platelet count ≥ 100,00/mm^3 Hemoglobin ≥ 9 g/dL WBC ≥ 2,000/mm^3 Creatinine ≤ 2 times upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Able to undergo radiotherapy, based on radiation oncology consultation Willing and able to comply with study treatment FEV_1 ≥ 1 L No requirement for daily supplemental oxygen No second primary malignancy, except for any of the following: Carcinoma in situ of the cervix Nonmelanoma skin cancer History of low-grade (Gleason score ≤ 6) localized prostate cancer, even if diagnosed within the past 5 years Stage I breast cancer that was treated within the past 5 years Other malignancy that was diagnosed and definitely treated ≥ 5 years ago with no subsequent evidence of recurrence No concurrent severe and/or uncontrolled medical condition, including any of the following: Angina pectoris Congestive heart failure within the past 3 months, unless LVEF > 40% Myocardial infarction within the past 6 months Cardiac arrhythmia No clinically significant infection No psychiatric illness or social situation that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior therapy for this cancer other than 2-6 courses of standard platinum-based chemotherapy with or without bevacizumab No prior radiotherapy to the treatment sites (e.g., primary lesion, clinically involved nodes, or metastatic lesions) No bevacizumab during and for 4 weeks after completion of radiotherapy No concurrent systemic chemotherapy No other maintenance systemic therapy during radiotherapy No other concurrent investigational agents for the primary neoplasm No concurrent intensity modulated radiotherapy No concurrent prophylactic nodal radiotherapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Arm I<br>Patients undergo observation for 6 weeks. | Other: clinical observation<br>* Patients undergo observation for 6 weeks.<br>|
| Experimental: Arm II<br>Patients undergo radiotherapy 5 days a week for 6 weeks to all sites of gross disease. | Radiation: radiation therapy<br>* Patients undergo radiotherapy 5 days a week for 6 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall survival was defined as the time from registration to the date of death or last follow-up | Time from registration to death or last follow-up (up to 5 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | A confirmed tumor response was defined as a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluations around 3 months apart. All participants with measurable disease (non-CR at baseline, etc.), meeting the eligibility criteria who have signed a consent form and have started the study were evaluable for response. | Up to 5 years | 
| Progression-free Survival | Progression-free survival was defined as the time from randomization to the first of either death due to any cause or progression. | Time from registration to disease progression or death (up to 5 years) | 
| Time to Disease Progression | Time to disease progression was defined as the time from randomization to the earliest date documentation of disease progression occurs. If a patient dies without a documentation of disease progression, the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. | Time from registration to disease progression (up to 5 years) | 
| Time to Treatment Failure | Time to treatment failure was defined as the time from the date of randomization to the date at which the patient was removed from treatment (Arm II) or no treatment (Arm I) due to progression, adverse events, or refusal. | Up to 5 years | 
| Duration of Response | Duration of response was defined for all evaluable patients who have achieved an objective response as the date at which the patient's earliest best objective status was first noted to be either a complete response (CR) or partial response (PR) to the earliest date progression was documented. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV non-small cell lung cancer, adenosquamous cell lung cancer, squamous cell lung cancer, large cell lung cancer, adenocarcinoma of the lung, bronchoalveolar cell lung cancer