Metastatic Lung CancerPhase 3NCT03867175
Immunotherapy With or Without SBRT in Patients With Stage IV Non-small Cell Lung Cancer
A Phase 3 study testing Stereotactic Body Radiation Therapy and Pembrolizumab in people with Metastatic Lung Cancer and Stage IV Lung Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Lung Cancer, Stage IV Lung Cancer
- What is being tested?
- Stereotactic Body Radiation Therapy and Pembrolizumab
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jun 2019to 21 Apr 2025
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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 exclusion criteria.
- Patients with major activating mutations in EGFR (del19, L858R, and T790M) or ROS 1 or ALK gene rearrangements are excluded
- Eligibility for Randomization
- Once enrolled on study, patients will have a PET/MRI brain for restaging. Patients with no evidence of progression and 8 or fewer sites of active persistent disease per the treating physician are eligible for randomization.
- If a PET has been performed within 30 days of enrollment with no evidence of progression per RECIST v1.1, then this scan may be used and does not have to be repeated prior to randomization.
- If an MRI brain has been performed within 90 days of enrollment with no evidence of progression per RECIST v1.1, then this scan may be used and does not have to be repeated prior to randomization.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: 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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To compare progression-free survival of patients randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone.
SECONDARY OBJECTIVES:
- 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.
- Conditions
- Metastatic Lung Cancer, Stage IV Lung Cancer
- Being tested
- Stereotactic Body Radiation Therapy, Pembrolizumab
- Medical subject headings
- Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Body Radiation TherapyRadiation
Also called Stereotactic Ablative Body Radiation Therapy
Patients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT)
PembrolizumabBiological
Also called Keytruda, Lambrolizumab, MK-3475, SCH 900475
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Experimental | 3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion. Receives: Radiation: Stereotactic Body Radiation Therapy; Biological: Pembrolizumab |
| Arm 2 Pembrolizumab Only | Experimental | Patients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician. Receives: Biological: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 5 years
Secondary outcomes (5)
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.
Measured: Up to 5 years
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.
Measured: Baseline up to 5 years
Number of Participants to Have a Rate of Failure
Investigators will assess the rate of failures inside and outside of radiation treatment.
Measured: Baseline up to 5 years
Number of Participants With New Sites of Disease
Investigators will assess the development of new sites of disease during or after immunotherapy
Measured: Baseline up to 5 years
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.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Mar 2019
- Study start24 Jun 2019
- Primary completion21 Apr 2025
- Study completion21 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Metastatic Lung CancerStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Michael Farris, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03867175
- Sponsor's protocol ID
- IRB00056681
- Other IDs
- NCI-2019-01259, CCCWFU 62718, P30CA012197
- Status last verified
- May 2025
- First submitted
- 5 Mar 2019
- Last updated
- 13 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT03867175
- Acronym / sponsor ID
- IRB00056681
- Conditions
- Metastatic Lung Cancer, Stage IV Lung Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 24 Jun 2019 (actual)
- Primary completion
- 21 Apr 2025 (actual)
- Study completion
- 21 Apr 2025 (actual)
- First posted
- 7 Mar 2019 (actual)
- Results
- Posted 13 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To compare progression-free survival of patients randomized to radiation and consolidative immunotherapy against those receiving consolidative immunotherapy alone.
SECONDARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab | Experimental | Radiation: Stereotactic Body Radiation Therapy, Biological: Pembrolizumab3-10 treatments of SBRT/ pembrolizumab IV for 30 minutes every 3-4 weeks for 1 year at doctor's discretion. |
| Arm 2 Pembrolizumab Only | Experimental | Biological: PembrolizumabPatients receive pembrolizumab IV over 30 minutes every 3-4 weeks for 1 year at the discretion of the treating physician. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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 exclusion criteria.
- Patients with major activating mutations in EGFR (del19, L858R, and T790M) or ROS 1 or ALK gene rearrangements are excluded
- Eligibility for Randomization
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Body Radiation TherapyAlso: Stereotactic Ablative Body Radiation TherapyPatients undergo 3-10 treatments of stereotactic body radiation therapy (SBRT) | Radiation | Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab |
| PembrolizumabAlso: Keytruda, Lambrolizumab, MK-3475, SCH 900475Patients 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. | Biological | Arm 1 Stereotactic Body Radiation Therapy/Pembrolizumab, Arm 2 Pembrolizumab Only |
Primary outcome
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.
5 secondary outcomes
Number of Participants With Overall Survival
Time frame: Up to 5 years
Number of Participants With Progression
Time frame: Baseline up to 5 years
Number of Participants to Have a Rate of Failure
Time frame: Baseline up to 5 years
Number of Participants With New Sites of Disease
Time frame: Baseline up to 5 years
Number of Participants With Adverse Events
Time frame: Up to 5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Farris, MD principal investigator
Wake Forest University Health Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Stereotactic Body Radiation Therapy and Pembrolizumab in people with Metastatic Lung Cancer and Stage IV Lung Cancer, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Progression-free Survival (PFS) After Completion of First Line Standard of Care Systemic Therapy (time frame: Up to 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jun 2025.