Recurrent Lung Non-Small Cell Carcinoma, Stage IV Non-Small Cell Lung Cancer AJCC v7
Conditions
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.
Interventions
OTHERClinical Observation
Undergo clinical observation
RADIATIONExternal Beam Radiation Therapy
Undergo EBRT
OTHERLaboratory Biomarker Analysis
Optional correlative studies
OTHERQuality-of-Life Assessment
Ancillary studies
PROCEDUREStandard Follow-Up Care
Undergo standard maintenance therapy
PROCEDURETherapeutic Conventional Surgery
Undergo surgery
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Canada, United States
Participant flow
Recruitment details
Dates of recruitment period: 11/28/2012 to 02/01/2016 ; Location: Multi-center trial that recruited patients at three different hospital sites (MD Anderson Cancer Center, Houston, TX; London Health Sciences Center, London, Ontario; and The University of Colorado, Aurora, CO) 9 patients in the MT/O group received LCT after progression. The remaining 15 did not.
Pre-assignment details
Three patients in the MT/O arm who crossed over to receive LCT before progression were excluded because they did not adhere to either arm of the study.
Participants by arm
| Arm | Count |
|---|---|
| LCT Arm LCT with radiation therapy or surgery followed by standard maintenance or observation | 25 |
| MT/O Arm Standard maintenance (chosen by the treating physician from predefined set of standard of care options) or observation | 24 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 11 | 18 |
Baseline characteristics
| Characteristic | LCT Arm | Total | MT/O Arm |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 21 Participants | 10 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants | 28 Participants | 14 Participants |
| Age, Continuous | 63 Years | 61 Years | 61 Years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 2 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants | 47 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Patient Characteristics | 25 participants | 49 participants | 24 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 38 Participants | 18 Participants |
| Region of Enrollment United States | 25 participants | 49 participants | 24 participants |
| Sex: Female, Male Female | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Male | 12 Participants | 22 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 25 | 18 / 24 |
| other Total, other adverse events | 14 / 25 | 12 / 24 |
| serious Total, serious adverse events | 0 / 25 | 0 / 24 |
Outcome results
Primary
Progression-free Survival (PFS)
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.
Time frame: 16.6 months to 41.2 months for all patients in both LCT and MT/O group
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LCT Arm | Progression-free Survival (PFS) | 14.2 Months |
| MT/O Arm | Progression-free Survival (PFS) | 4.4 Months |
Secondary
Time to New Lesion Progression
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.
Time frame: 5.7 to 24.3 months (LCT group); 4.4 to 8.3 months (MT/O group)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| LCT Arm | Time to New Lesion Progression | 14.2 Months |
| MT/O Arm | Time to New Lesion Progression | 6 Months |