Surgery and/or Radiation Therapy or Standard Therapy and/or Clinical Observation in Treating Patients With Previously Treated Stage IV Non-small Cell Lung Cancer

Phase 2

Completed

Conditions: Recurrent Lung Non-Small Cell Carcinoma
Stage IV Non-Small Cell Lung Cancer AJCC v7

Interventions: Radiation: External Beam Radiation Therapy
Other: Clinical Observation
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Procedure: Therapeutic Conventional Surgery
Procedure: Standard Follow-Up Care

Registration Number: NCT01725165

Lead Sponsor: M.D. Anderson Cancer Center

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 85

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
STEP 2 ENROLLMENT AND RANDOMIZATION: platelet count >= 100,000/mm^3 within 3 weeks of study entry
STEP 2 ENROLLMENT AND RANDOMIZATION: white blood cells (WBC) >= 3,000/mm^3 within 3 weeks of study entry
STEP 2 ENROLLMENT AND RANDOMIZATION: hemoglobin >= 9 g/dL within 3 weeks of study entry
STEP 2 ENROLLMENT AND RANDOMIZATION: the patient must be a suitable candidate for LCT (radiotherapy and/or surgery) to every site of disease, as determined by the treating physician(s); consultation with a multidisciplinary team, including a medical oncologist, radiation oncologist, and thoracic surgeon, is encouraged but not required
STEP 2 ENROLLMENT AND RANDOMIZATION: concurrent chemoradiation is permitted as consolidative therapy; the following concurrent therapies are permitted: tyrosine kinase inhibitors (i.e. erlotinib) - can be delivered with both hypofractionated (>= 3 Gray [Gy] per fraction) and standard fractionated radiation therapy (< 3 Gy per fraction); platinum-based chemotherapy - standard fractionated radiation therapy (< 3 Gy per fraction)
STEP 2 ENROLLMENT AND RANDOMIZATION: bevacizumab will not be permitted within 2 weeks of the initiation of the radiation therapy course
STEP 2 ENROLLMENT AND RANDOMIZATION: treatment to central nervous system lesions, such as the brain or spine (prior to first line systemic therapy), or symptomatic lesions requiring urgent palliative radiation, is permitted prior to randomization, in which case the patient would be randomized to treatment of other metastatic sites or the primary sites (based on the disease remaining after first-line treatment); these treated lesions should be counted towards the total number of metastases at the time of enrollment
STEP 2 ENROLLMENT AND RANDOMIZATION: the patient has signed informed consent
STEP 2 ENROLLMENT AND RANDOMIZATION: women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation and for six (6) months after discontinuation of the study drugs; childbearing potential will be defined as women who have had menses within the past 12 months, who have not had tubal ligation, hysterectomy or bilateral oophorectomy; should a woman become pregnant or suspect that she is pregnant while participating in this study, she should inform her treating physician immediately; the patient, if a man, agrees to use effective contraception or abstinence for the duration of study participation and for six (6) months after discontinuation of the study drugs

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Arm I (immediate LCT)	Therapeutic Conventional Surgery	Patients undergo ablation of all residual local and metastatic sites of disease by surgery and/or EBRT. After completion of LCT, patients undergo either surveillance or maintenance treatment at the discretion of the treating physician.
Arm II (delayed/no LCT)	Quality-of-Life Assessment	Patients undergo standard maintenance therapy or clinical observation, based on physician choice. Patients may cross-over to Arm I due to RECIST progression or toxicity at the treating physician's discretion.
Arm I (immediate LCT)	Laboratory Biomarker Analysis	Patients undergo ablation of all residual local and metastatic sites of disease by surgery and/or EBRT. After completion of LCT, patients undergo either surveillance or maintenance treatment at the discretion of the treating physician.
Arm I (immediate LCT)	External Beam Radiation Therapy	Patients undergo ablation of all residual local and metastatic sites of disease by surgery and/or EBRT. After completion of LCT, patients undergo either surveillance or maintenance treatment at the discretion of the treating physician.
Arm II (delayed/no LCT)	Clinical Observation	Patients undergo standard maintenance therapy or clinical observation, based on physician choice. Patients may cross-over to Arm I due to RECIST progression or toxicity at the treating physician's discretion.
Arm I (immediate LCT)	Quality-of-Life Assessment	Patients undergo ablation of all residual local and metastatic sites of disease by surgery and/or EBRT. After completion of LCT, patients undergo either surveillance or maintenance treatment at the discretion of the treating physician.
Arm II (delayed/no LCT)	Laboratory Biomarker Analysis	Patients undergo standard maintenance therapy or clinical observation, based on physician choice. Patients may cross-over to Arm I due to RECIST progression or toxicity at the treating physician's discretion.
Arm II (delayed/no LCT)	Standard Follow-Up Care	Patients undergo standard maintenance therapy or clinical observation, based on physician choice. Patients may cross-over to Arm I due to RECIST progression or toxicity at the treating physician's discretion.

Primary Outcome Measures

Name	Time	Method
Progression-free Survival (PFS)	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 Outcome Measures

Name	Time	Method
Time to New Lesion Progression	5.7 to 24.3 months (LCT group); 4.4 to 8.3 months (MT/O group)	The measurement of time to new lesion progression of patients from the start of trial participation until the time their disease progresses. 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.

Trial Locations

Locations (3): University of Colorado
🇺🇸
Denver, Colorado, United States
M D Anderson Cancer Center
🇺🇸
Houston, Texas, United States
London Health Sciences Centre-South Street
🇨🇦
London, Ontario, Canada