Metastatic Lung Cancer, Stage IV Lung Cancer
Conditions
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.
Interventions
RADIATIONStereotactic Body Radiation Therapy
Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT)
BIOLOGICALPembrolizumab
Patients undergo 3-10 treatments of SBRT. Patients also receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician.
Sponsors
National Cancer Institute (NCI)
Wake Forest University Health Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 v1.1. * 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 1. 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 * More than 180 days has elapsed since day 1 of cycle 1 of standard of care systemic therapy. * Pregnant or lactating women. * The patient has received treatment for other carcinomas within the last three years (Except for cured non-melanoma skin cancer, low-risk prostate cancer, T1/T2 glottic cancer, stage 0 or stage I breast cancer, non-invasive bladder cancer, or treated in-situ cervical cancer). Prior lung cancer diagnosis now with oligometastatic recurrence is not an
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy | 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Overall Survival | Up to 5 years | Overall Survival is defined as the duration from the start of first line standard of care systemic therapy to the date of death or date of last contact; those lost to follow-up will be censored and will be reported with an exact 95% confidence interval. |
| Number of Participants With Progression | Baseline up to 5 years | In patients not receiving radiation, the investigators will assess progression at their known sites of disease prior to beginning first line systemic chemotherapy. |
| Number of Participants to Have a Rate of Failure | Baseline up to 5 years | Investigators will assess the rate of failures inside and outside of radiation treatment. |
| Number of Participants With New Sites of Disease | Baseline up to 5 years | Investigators will assess the development of new sites of disease during or after immunotherapy |
| Number of Participants With Adverse Events | Up to 5 years | All safety measures, including acute and late toxicity, will be reported using descriptive statistics (mean, median, standard deviation, proportions, and 95% confidence intervals). This will include calculating frequency/risk of adverse events by treatment site. Potential toxicities reported would include pneumonitis, esophagitis, chest wall pain, dermatologic toxicity, renal dysfunction, gastrointestinal toxicity including nausea, vomiting, and diarrhea, hepatotoxicity, and abdominal pain. These toxicities would be assessed according to site of irradiation by the treating physician and graded as per Common Terminology Criteria for Adverse Events 5. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 4 |
| 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. | 1 |
| Total | 5 |
Baseline characteristics
| Characteristic | Arm 2 Pembrolizumab Only | Total | Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab |
|---|---|---|---|
| Age, Continuous | 53 years | 59.8 years STANDARD_DEVIATION 9.4 | 61.5 years STANDARD_DEVIATION 9.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 5 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 4 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 4 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 1 / 1 |
| serious Total, serious adverse events | 2 / 4 | 1 / 1 |
Outcome results
Primary
Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy
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.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy | 1 Participants |
| Arm 2 Pembrolizumab Only | Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy | 0 Participants |
Secondary
Number of Participants to Have a Rate of Failure
Investigators will assess the rate of failures inside and outside of radiation treatment.
Time frame: Baseline up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Number of Participants to Have a Rate of Failure | 1 Participants |
| Arm 2 Pembrolizumab Only | Number of Participants to Have a Rate of Failure | 0 Participants |
Secondary
Number of Participants With Adverse Events
All safety measures, including acute and late toxicity, will be reported using descriptive statistics (mean, median, standard deviation, proportions, and 95% confidence intervals). This will include calculating frequency/risk of adverse events by treatment site. Potential toxicities reported would include pneumonitis, esophagitis, chest wall pain, dermatologic toxicity, renal dysfunction, gastrointestinal toxicity including nausea, vomiting, and diarrhea, hepatotoxicity, and abdominal pain. These toxicities would be assessed according to site of irradiation by the treating physician and graded as per Common Terminology Criteria for Adverse Events 5.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Number of Participants With Adverse Events | 4 Participants |
| Arm 2 Pembrolizumab Only | Number of Participants With Adverse Events | 1 Participants |
Secondary
Number of Participants With New Sites of Disease
Investigators will assess the development of new sites of disease during or after immunotherapy
Time frame: Baseline up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Number of Participants With New Sites of Disease | 1 Participants |
| Arm 2 Pembrolizumab Only | Number of Participants With New Sites of Disease | 0 Participants |
Secondary
Number of Participants With Overall Survival
Overall Survival is defined as the duration from the start of first line standard of care systemic therapy to the date of death or date of last contact; those lost to follow-up will be censored and will be reported with an exact 95% confidence interval.
Time frame: Up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Number of Participants With Overall Survival | 1 Participants |
| Arm 2 Pembrolizumab Only | Number of Participants With Overall Survival | 0 Participants |
Secondary
Number of Participants With Progression
In patients not receiving radiation, the investigators will assess progression at their known sites of disease prior to beginning first line systemic chemotherapy.
Time frame: Baseline up to 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Number of Participants With Progression | 1 Participants |
| Arm 2 Pembrolizumab Only | Number of Participants With Progression | 0 Participants |