A Randomized Phase II Study Assessing the Efficacy of Local Consolidative Therapy for Non-Small Cell Lung Cancer Patients With Induced Oligometastatic Disease
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Recurrent Lung Non-Small Cell Carcinoma
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 85
- Locations
- 3
- Primary Endpoint
- Progression-free Survival (PFS)
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
This randomized phase II trial studies how well surgery and/or radiation therapy or standard therapy and/or clinical observation works in treating patients with previously treated stage IV non-small cell lung cancer. Radiation therapy uses high energy x-rays to kill tumor cells. Giving surgery and/or radiation therapy may be more effective than standard therapy and/or clinical observation in patients with previously treated non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. Determine whether oligometastatic non-small cell lung cancer (NSCLC) patients with no disease progression after first line therapy have prolonged progression free survival (PFS) when treated with local consolidation therapy (LCT) of residual disease (radiation or surgery) followed by maintenance or surveillance as per physician choice compared with no LCT. SECONDARY OBJECTIVES: I. Determine the overall survival. II. Safety/tolerability of LCT. III. Time to progression of prior metastatic lesions. IV. Time to appearance of new metastases (central nervous system \[CNS\] vs. extra-CNS, treated lesion vs. new site). V. Quality of life (QOL). OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I (IMMEDIATE LCT): Patients undergo ablation of all residual local and metastatic sites of disease by surgery and/or external beam radiation therapy (EBRT). After completion of LCT, patients undergo either surveillance or maintenance treatment at the discretion of the treating physician. ARM II (DELAYED/NO LCT): Patients undergo standard maintenance therapy or clinical observation, based on physician choice. Patients may cross-over to Arm I due to Response Evaluation Criteria in Solid Tumors (RECIST) progression or toxicity at the treating physician's discretion. After completion of study treatment, patients are followed up for 9 months.
Investigators
Eligibility Criteria
Inclusion Criteria
- •STEP 1 ENROLLMENT: the patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration; mixed tumors will be categorized by the predominant cell type
- •STEP 1 ENROLLMENT: the patient has a diagnosis of American Joint Committee on Cancer (AJCC) 7th Edition stage IV NSCLC
- •STEP 1 ENROLLMENT: three or less metastatic lesions (not sites); each lesion (including a satellite nodule) will individually be counted as one, and intrathoracic lymph node involvement (defined here as hilar, mediastinal, or supraclavicular nodes, N1-N3) will collectively be counted as one; in addition, patients can receive treatment to CNS lesions or other symptomatic lesions requiring urgent local therapy prior to randomization, but these lesions will be counted towards the total number after chemotherapy, and patients will only be eligible if there are remaining sites amenable to local therapy after up-front systemic therapy
- •STEP 1 ENROLLMENT: standard induction chemotherapy planned defined as: at least 4 cycles of platinum doublet chemotherapy for metastatic disease (with or without bevacizumab); if the patient is known to be EGFR mutation positive, erlotinib, afatinib, or gefitinib for \>= 3 months, or for patients with known EML4-ALK fusions, crizotinib for \>= 3 months
- •STEP 2 ENROLLMENT AND RANDOMIZATION: the patient has a diagnosis of pathologically confirmed NSCLC by tumor biopsy and/or fine-needle aspiration; mixed tumors will be categorized by the predominant cell type
- •STEP 2 ENROLLMENT AND RANDOMIZATION: the patient has a diagnosis of American Joint Committee on Cancer (AJCC) 7th edition stage IV NSCLC
- •STEP 2 ENROLLMENT AND RANDOMIZATION: completion of standard induction chemotherapy planned defined as: at least 4 cycles of platinum doublet chemotherapy for metastatic disease (with or without bevacizumab); if the patient is known to be EGFR mutation positive, erlotinib, afatinib, or gefitinib for \>= 3 months, or for patients with known EML4-ALK fusions, crizotinib; note that it is not mandatory to check EGFR mutation or EML4-ALK status prior to entry, but patients that receive options 2 or 3 should have had these molecular tests performed
- •STEP 2 ENROLLMENT AND RANDOMIZATION: less than or equal to three metastatic lesions and no evidence of disease progression based on RECIST criteria; note that patients that had \> 3 metastatic lesions in Step 1 may be eligible for enrollment in Step 2 if the number of metastatic sites is reduced to three or less
- •STEP 2 ENROLLMENT AND RANDOMIZATION: the patient's Eastern Cooperative Oncology Group (ECOG) performance status is =\< 2 at study entry
- •STEP 2 ENROLLMENT AND RANDOMIZATION: absolute neutrophil count (ANC) \>= 1,500/mm\^3 within 3 weeks of study entry
Exclusion Criteria
- •STEPS 1 AND 2 AND RANDOMIZATION
- •The patient has a history of uncontrolled angina, arrhythmias, or congestive heart failure
- •Patients with a history of malignant pleural effusions are not eligible; pleural effusions considered by the investigator too small for a diagnostic thoracentesis are permissible
- •Patient is pregnant (confirmed by serum beta- b-human chorionic gonadotropin \[HCG\] if applicable) or is breastfeeding
- •Presence of significant third space fluid which cannot be controlled by drainage
Outcomes
Primary Outcomes
Progression-free Survival (PFS)
Time Frame: 16.6 months to 41.2 months for all patients in both LCT and MT/O group
The measurement of overall survival of patients from the start of trial participation until the time their disease progresses or death of the patient. The outcome measures were stratified per the randomization on protocol. The results were not reclassified based on later sequencing. This was all done in accordance to the protocol document.
Secondary Outcomes
- Time to New Lesion Progression(5.7 to 24.3 months (LCT group); 4.4 to 8.3 months (MT/O group))