A Randomized Trial of Consolidative Immunotherapy With vs Without Thoracic Radiotherapy and / or Stereotactic Body Radiation Therapy (SBRT) After First-Line Systemic Therapy for Metastatic NSCLC
Overview
- Phase
- Phase 3
- Intervention
- Stereotactic Body Radiation Therapy
- Conditions
- Metastatic Lung Cancer
- Sponsor
- Wake Forest University Health Sciences
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This phase III trial studies immunotherapy and stereotactic body radiation therapy to see how well it works compared with immunotherapy alone after first-line systemic therapy (therapy that goes throughout the body) in treating patients with stage IV non-small cell lung cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Giving immunotherapy with stereotactic body radiation therapy may work better than immunotherapy alone in treating patients with non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To compare progression-free survival of patients randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone. SECONDARY OBJECTIVES: I. To estimate overall survival in all patients and will compare overall survival of those randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone. II. In patients receiving radiation, to describe the rate of in-field local control and rate of out-of-field disease progression with serial imaging. III. In patients not receiving radiation, describe progression at known sites of disease after first line systemic therapy and rate of development of new metastases with serial imaging. IV. To evaluate toxicity associated with radiation followed by consolidative immunotherapy. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT). Patients also receive pembrolizumab intravenously (IV) over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician. ARM II: Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician. After completion of study treatment, patients are followed up at 1 month, every 3 months for 1 year, every 6 months for the next 2 years, and then annually for 2 years.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients who are 18 years or older.
- •Performance Status 0-2 (ECOG) at time of consult with radiation oncology.
- •Pathologically proven non-small cell lung cancer (NSCLC) with evidence of metastatic disease.
- •Must have received 4 cycles of standard of care systemic therapy (usually this will consist of combination chemo-immunotherapy), with a CT chest abdomen pelvis that was performed after completion of these 4 cycles and demonstrates no evidence of progression per RECIST v1.
- •To be eligible for enrollment and randomization, patients must be within 180 days from their first dose of standard of care systemic therapy. Cycle 1 day 1 is defined as day
- •If enrolled on day 180, the patient would need to be randomized the same day.
- •Persistent active disease must be amenable to radiation treatment per the treating radiation oncologist, and patients must have at least one residual site of disease which can be identified by CT or PET/CT and targeted with radiation.
- •Patients who previously had earlier stage NSCLC treated definitively and have now developed new distant disease, are eligible for inclusion if they have undergone at least 4 cycles of standard of care systemic therapy for their metastatic recurrence, and they meet all criteria above.
- •There are no strict size or tumor number limitations in a given organ (lung, liver, abdomen pelvis, or spine). This is at the discretion of the treating radiation oncologist.
- •Exclusion Criteria from Enrollment
Exclusion Criteria
- Not provided
Arms & Interventions
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab
3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion.
Intervention: Stereotactic Body Radiation Therapy
Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab
3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion.
Intervention: Pembrolizumab
Arm 2 Pembrolizumab Only
Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy
Time Frame: Up to 5 years
Will be determined using the product-limit method of Kaplan and Meier. Will compare unadjusted median PFS between the 2 arms using a log-rank test. Will also use a proportional hazards model to compare progression-free survival between the two groups, adjusting for key covariates such as age, performance (Eastern Cooperative Oncology Group) status, response to initial systemic therapy versus (vs) stable disease, the presence or absence of brain metastases, PD-L1 \[programmed death-ligand \] expression (\< 1% vs \> 50%), tumor histology (adenocarcinoma vs non-adenocarcinoma), and number of disease sites treated (1-3 sites vs 4-6 sites). Progression is defined using RECIST v1.1 is relative Increase: A 20% increase in the sum of the longest diameters of target lesions (from baseline or nadir) is a criterion for PD.
Secondary Outcomes
- Number of Participants With Overall Survival(Up to 5 years)
- Number of Participants With Progression(Baseline up to 5 years)
- Number of Participants to Have a Rate of Failure(Baseline up to 5 years)
- Number of Participants With New Sites of Disease(Baseline up to 5 years)
- Number of Participants With Adverse Events(Up to 5 years)