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

• ClinicalTrials.gov Identifier: NCT01725165
• Recruitment Status: Completed
• First Posted: November 12, 2012
• Last Update Posted: May 13, 2024
• Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by (Responsible Party): M.D. Anderson Cancer Center

Tracking Information

• First Submitted Date: November 8, 2012
• First Posted Date: November 12, 2012
• Last Update Posted Date: May 13, 2024
• Actual Study Start Date: November 28, 2012
• Actual Primary Completion Date: May 8, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 7, 2019)

Progression-free survival (PFS) [ Time Frame: Time from randomization (immediate local consolidation therapy [LCT] vs delayed/no LCT) to disease progression or death, assessed up to 9 months ]

Kaplan-Meier estimate will be computed and the log-rank test will be performed to compare the difference of PFS between the two arms. Cox regression model will be applied to correlate PFS with potential covariates in both the univariate and multi-covariate analyses. To account for patients that crossover for reasons other than Response Evaluation Criteria in Solid Tumors (RECIST) progression of disease, censoring will occur at the time of crossover for primary analysis.

Original Primary Outcome Measures (submitted: November 8, 2012)

Progression-Free Survival (PFS) [ Time Frame: 4 months ]

Progression-free survival (PFS) defined as time from the time of randomization (LCT vs. no LCT) to disease progression or death. For the primary endpoint, PFS, Kaplan-Meier estimate will be computed and the log-rank test will be performed to compare the difference of PFS between the two arms.

Current Secondary Outcome Measures (submitted: May 7, 2019)

• Incidence of toxicities [ Time Frame: Up to at least 1 year (periodically thereafter) ]
  Descriptive statistics will be provided to summarize the toxicities by the treatment arms (immediate LCT and delayed/no LCT groups).
• Overall survival [ Time Frame: Up to 9 months ]
  Kaplan-Meier estimate will be used.
• Time to progression of prior metastatic lesions [ Time Frame: Up to 9 months ]
  Kaplan-Meier estimate will be used.
• Time to appearance of new metastases (central nervous system [CNS] vs extra-CNS, treated lesion vs. new site) [ Time Frame: Up to 9 months ]
  Kaplan-Meier estimate will be used.
• Quality of life (QOL) assessed using the Symptom Assessment (optional) [ Time Frame: Up to 1 year ]
  QOL will be analyzed by the repeated measures analysis of variance to count for the change before and after treatment and during the follow-up period. Proper transformation will be performed if necessary to transform data to be closer to the Gaussian distribution.
• Impact of crossover without RECIST progression [ Time Frame: Up to 9 months ]
  A time varying covariate model will be used.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: A Randomized Phase II Study Assessing the Efficacy of Local Consolidative Therapy for Non-Small Cell Lung Cancer Patients With Induced Oligometastatic Disease
• 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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Other: Clinical Observation
  Undergo clinical observation
  Other Name: observation
• Radiation: External Beam Radiation Therapy
  Undergo EBRT
  Other Names:

  • Definitive Radiation Therapy
  • EBRT
  • External Beam Radiotherapy
  • External Beam RT
  • external radiation
  • External Radiation Therapy
  • external-beam radiation
• Other: Laboratory Biomarker Analysis
  Optional correlative studies
• Other: Quality-of-Life Assessment
  Ancillary studies
  Other Name: Quality of Life Assessment
• Procedure: Standard Follow-Up Care
  Undergo standard maintenance therapy
• Procedure: Therapeutic Conventional Surgery
  Undergo surgery

Study Arms

• Experimental: Arm I (immediate LCT)
  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.
  Interventions:

  • Radiation: External Beam Radiation Therapy
  • Other: Laboratory Biomarker Analysis
  • Other: Quality-of-Life Assessment
  • Procedure: Therapeutic Conventional Surgery
• Active Comparator: 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 RECIST progression or toxicity at the treating physician's discretion.
  Interventions:

  • Other: Clinical Observation
  • Other: Laboratory Biomarker Analysis
  • Other: Quality-of-Life Assessment
  • Procedure: Standard Follow-Up Care

Publications *

• Tang C, Lee WC, Reuben A, Chang L, Tran H, Little L, Gumbs C, Wargo J, Futreal A, Liao Z, Xia X, Yi X, Swisher SG, Heymach JV, Gomez D, Zhang J. Immune and Circulating Tumor DNA Profiling After Radiation Treatment for Oligometastatic Non-Small Cell Lung Cancer: Translational Correlatives from a Mature Randomized Phase II Trial. Int J Radiat Oncol Biol Phys. 2020 Feb 1;106(2):349-357. doi: 10.1016/j.ijrobp.2019.10.038. Epub 2019 Oct 31.
• Gomez DR, Blumenschein GR Jr, Lee JJ, Hernandez M, Ye R, Camidge DR, Doebele RC, Skoulidis F, Gaspar LE, Gibbons DL, Karam JA, Kavanagh BD, Tang C, Komaki R, Louie AV, Palma DA, Tsao AS, Sepesi B, William WN, Zhang J, Shi Q, Wang XS, Swisher SG, Heymach JV. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016 Dec;17(12):1672-1682. doi: 10.1016/S1470-2045(16)30532-0. Epub 2016 Oct 24.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 29, 2023): 85
• Original Estimated Enrollment (submitted: November 8, 2012): 94
• Actual Study Completion Date: May 8, 2024
• Actual Primary Completion Date: May 8, 2024 (Final data collection date for primary outcome measure)

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
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT01725165
• Other Study ID Numbers: 2012-0618; NCI-2012-02874 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2012-0618 ( Other Identifier: M D Anderson Cancer Center )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: M.D. Anderson Cancer Center
• Original Responsible Party: Same as current
• Current Study Sponsor: M.D. Anderson Cancer Center
• Original Study Sponsor: Same as current
• Collaborators: National Cancer Institute (NCI)

Investigators

• Principal Investigator: Chad Tang; M.D. Anderson Cancer Center

• PRS Account: M.D. Anderson Cancer Center
• Verification Date: May 2024