Stage IV Non-Small Cell Lung CancerNCT03176173
Radical RADiotherapy and Immunotherapy for Metastatic CAncer of the Lung (RRADICAL)
A study testing Image-guided Radiation Therapy in people with Stage IV Non-Small Cell Lung Cancer, run by Stanford University at 1 site in United States.
Trial summary
This phase II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IV Non-Small Cell Lung Cancer
- What is being tested?
- Image-guided Radiation Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jun 2017to 31 Jan 2025
- Phase
- Interventional
- 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
- Has stage IV non-small cell lung cancer, or initially stage I-III disease with distant metastatic recurrence
- Age ≥ 18
- Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks (refer to section 4.2.1)
- Has had restaging imaging after initiation of immunotherapy, at least 4 weeks after pre-immunotherapy baseline imaging. CT or PET/CT of at least chest/upper abdomen must be performed within 4 weeks prior to registration. For patients with history of brain metastases, brain MRI or CT is required within 4 weeks of registration; for other patients brain MRI or CT is required within 12 weeks of registration. Diagnostic PET/CT performed as part of radiation simulation can be used as the restaging imaging.
- Most recent imaging shows measurable disease as defined by RECIST 1.1
- Evaluation by a Stanford medical oncologist must show:
Show all 12Show fewer
- The patient is expected to continue on immunotherapy for at least three more months
- Imaging must show response, stable disease, or modest progression
- If there is modest progression, the patient must be clinically stable in terms of performance status and overall disease-related symptoms
- Has at least one extracranial tumor safely treatable with radical-dose radiation therapy and that has not been previously treated with radiation
- ECOG performance status 0-2
- Has the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Untreated brain metastases, if not planned to be treated in this course of radiation therapy
- Pregnancy or women of childbearing potential not willing/able to use contraception during protocol treatment
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University, School of Medicine
Palo Alto, California, 94304
About this study
Official title: Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy
This phase II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radical-dose image guided radiation therapy to patients with non-small cell lung cancer may help to improve response to immunotherapy anti-cancer treatment.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine if progression-free survival at 24 weeks with this treatment combination is improved compared to historical controls who received immunotherapy without radiation therapy.
SECONDARY OBJECTIVES:
- Assess acute (0-6 months) and late (> 6 months) grade 3-5 toxicity. II. Assess overall survival. III. Correlate circulating tumor deoxyribonucleic acid (DNA) (ratio of post-radiation therapy [RT] to pre-RT level) with radiographic response.
IV. Correlate immune markers in peripheral blood with radiographic response.
TERTIARY OBJECTIVES:
- Analyze progression-free survival with immune-related response criteria. II. Measure time to discontinuation of study immunotherapy agent. III. Assess patterns of progression.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while undergoing standard of care immunotherapy.
Arm II: Patients who decline to undergo radiation therapy receive standard of care immunotherapy.
After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.
- Conditions
- Stage IV Non-Small Cell Lung Cancer
- Being tested
- Image-guided Radiation Therapy, Immunotherapy (physician's choice for standard of care immunotherapy)
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Image-guided Radiation TherapyRadiation
Also called IGRT
Ablative treatment as 50 Gy in 5 or 10 fractions.
Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions.
Immunotherapy (physician's choice for standard of care immunotherapy)Drug
Also called biologic therapy
Continue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol.
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy plus Image-guided Radiation Therapy | Experimental | Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. Receives: Radiation: Image-guided Radiation Therapy; Drug: Immunotherapy (physician's choice for standard of care immunotherapy) |
| Immunotherapy Alone (Regular Medical Care) | Active comparator | Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy. Receives: Drug: Immunotherapy (physician's choice for standard of care immunotherapy) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Defined as percentage of participants without disease progression or death at 24 weeks from date of study entry, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Complete Response (CR): Disappearance of all target lesions
Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions
Overall Response (OR): CR + PR
Measured: 24 weeks from study entry
Secondary outcomes (4)
Change in Circulating Tumor Deoxyribonucleic Acid Levels as Measured Using CAncer Personalized Profiling by Deep Sequencing
Will correlate with radiographic response. Plasma biomarkers (e.g. cell free deoxyribonucleic acid level) will be summarized using medians and interquartile ranges; changes in biomarkers will be assessed using the Wilcoxon signed rank test. Correlation of biomarkers with radiographic response will be evaluated using a Wilcoxon rank sum test on patients with and without the event of interest. If feasible, these analyses will be supplemented by more formal analyses with the Cox model.
Measured: Baseline (pre-treatment)
Change in Immune Marker Levels as Measured From Peripheral Blood Using Flow Cytometry Performed by the Human Immune Monitoring Core at Stanford University
Change in immune marker levels was measured using flow cytometry performed by the Human Immune Monitoring Core at Stanford University. These changes will correlate with radiographic response.
Measured: Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)
Number of Participants With Acute (0-6 Months) and Late (> 6 Months) Grade 3-5 Toxicity
This outcome measured the number of participants who experienced Grade 3-5 acute (0-6 months) and late (>6 months) toxicities, assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 4, through up to 4 years after study entry.
Measured: Up to 4 years after study entry
Overall Survival
The electronic medical record was monitored for patient deaths.
Measured: Time from study entry to death, assessed up to 4 years after study entry
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2017
- Study start28 Jun 2017
- Primary completion24 Nov 2021
- Study completion31 Jan 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 Stage IV Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Varian Medical Systems
- Responsible party
- Principal investigator, Michael Francis Gensheimer, Stanford University
- Investigators
- Michael Gensheimer, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03176173
- Sponsor's protocol ID
- IRB-40088
- Other IDs
- NCI-2017-00952, LUN0088
- Status last verified
- Aug 2025
- First submitted
- 1 Jun 2017
- Last updated
- 5 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radical-Dose Image Guided Radiation Therapy in Treating Patients With Metastatic Non-small Cell Lung Cancer Undergoing Immunotherapy
- ClinicalTrials.gov ID
- NCT03176173
- Acronym / sponsor ID
- IRB-40088
- Conditions
- Stage IV Non-Small Cell Lung Cancer
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- Varian Medical Systems
- Study start
- 28 Jun 2017 (actual)
- Primary completion
- 24 Nov 2021 (actual)
- Study completion
- 31 Jan 2025 (actual)
- First posted
- 5 Jun 2017 (actual)
- Results
- Posted 5 Nov 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 II trial studies how well radical-dose image guided radiation therapy works in treating patients with non-small cell lung cancer that has spread to other places in the body who are undergoing immunotherapy. Radiation therapy uses high energy x-rays to kill tumor cells and shrink tumors. Giving radical-dose image guided radiation therapy to patients with non-small cell lung cancer may help to improve response to immunotherapy anti-cancer treatment.
Detailed description
PRIMARY OBJECTIVES:
- Determine if progression-free survival at 24 weeks with this treatment combination is improved compared to historical controls who received immunotherapy without radiation therapy.
SECONDARY OBJECTIVES:
- Assess acute (0-6 months) and late (> 6 months) grade 3-5 toxicity. II. Assess overall survival. III. Correlate circulating tumor deoxyribonucleic acid (DNA) (ratio of post-radiation therapy [RT] to pre-RT level) with radiographic response.
IV. Correlate immune markers in peripheral blood with radiographic response.
TERTIARY OBJECTIVES:
- Analyze progression-free survival with immune-related response criteria. II. Measure time to discontinuation of study immunotherapy agent. III. Assess patterns of progression.
OUTLINE: Patients are assigned to 1 of 2 arms.
ARM I: Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while undergoing standard of care immunotherapy.
Arm II: Patients who decline to undergo radiation therapy receive standard of care immunotherapy.
After completion of study treatment, patients are followed up at 30 days and every 6 months thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy plus Image-guided Radiation Therapy | Experimental | Radiation: Image-guided Radiation Therapy, Drug: Immunotherapy (physician's choice for standard of care immunotherapy)Patients undergo radical-dose image guided radiation therapy daily for up to 10 days (within 2 weeks) while continuing their prior treatment with the treating physician's choice of regular medical care immunotherapy. |
| Immunotherapy Alone (Regular Medical Care) | Active comparator | Drug: Immunotherapy (physician's choice for standard of care immunotherapy)Patients who decline to undergo radiation therapy will continue their prior treatment with the treating physician's choice of regular medical care immunotherapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Has stage IV non-small cell lung cancer, or initially stage I-III disease with distant metastatic recurrence
- Age ≥ 18
- Has been receiving anti-PD-1 or anti-PD-L1 immunotherapy for at least four weeks (refer to section 4.2.1)
- Has had restaging imaging after initiation of immunotherapy, at least 4 weeks after pre-immunotherapy baseline imaging. CT or PET/CT of at least chest/upper abdomen must be performed within 4 weeks prior to registration. For patients with history of brain metastases, brain MRI or CT is required within 4 weeks of registration; for other patients brain MRI or CT is required within 12 weeks of registration. Diagnostic PET/CT performed as part of radiation simulation can be used as the restaging imaging.
- Most recent imaging shows measurable disease as defined by RECIST 1.1
Key exclusion criteria (2 listed)
- Untreated brain metastases, if not planned to be treated in this course of radiation therapy
- Pregnancy or women of childbearing potential not willing/able to use contraception during protocol treatment
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 |
|---|---|---|
| Image-guided Radiation TherapyAlso: IGRTAblative treatment as 50 Gy in 5 or 10 fractions. Non-ablative treatment as 27 Gy in 3 fractions, or 40 Gy in 10 fractions. | Radiation | Immunotherapy plus Image-guided Radiation Therapy |
| Immunotherapy (physician's choice for standard of care immunotherapy)Also: biologic therapyContinue regular medical care immunotherapy. Other than being an anti-PD-1 or anti-PD-L1 immunotherapy, the agent, dose, and schedule is not specified by protocol. | Drug | Immunotherapy Alone (Regular Medical Care), Immunotherapy plus Image-guided Radiation Therapy |
Primary outcome
Progression-free Survival
Time frame: 24 weeks from study entry
Defined as percentage of participants without disease progression or death at 24 weeks from date of study entry, assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete Response (CR): Disappearance of all target lesions Partial Response (PR): ≥30% decrease in the sum of the longest diameter of target lesions Overall Response (OR): CR + PR
4 secondary outcomes
Change in Circulating Tumor Deoxyribonucleic Acid Levels as Measured Using CAncer Personalized Profiling by Deep Sequencing
Time frame: Baseline (pre-treatment)
Change in Immune Marker Levels as Measured From Peripheral Blood Using Flow Cytometry Performed by the Human Immune Monitoring Core at Stanford University
Time frame: Pre-radiation (up to 14 days before RT) and post-radiation (up to 14 days after completion of RT)
Number of Participants With Acute (0-6 Months) and Late (> 6 Months) Grade 3-5 Toxicity
Time frame: Up to 4 years after study entry
Overall Survival
Time frame: Time from study entry to death, assessed up to 4 years after study entry
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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 Gensheimer principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Image-guided Radiation Therapy in people with Stage IV Non-Small Cell Lung Cancer, run by Stanford University 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 12 inclusion and 2 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 5 Nov 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Nov 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?
Progression-free Survival (time frame: 24 weeks from study entry). 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 5 Nov 2025.