Non-small Cell Lung Cancer MetastaticPhase 2NCT02314364
A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC
A Phase 2 study testing SBRT with protons or photons in people with Non-small Cell Lung Cancer Metastatic and Targetable Oncogenes (EGFR, ALK, ROS1), run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This research study is studying a type of radiation therapy called Stereotactic Body Radiation Therapy (SBRT) as a possible treatment for stage IV non-small cell lung cancer (NSCLC) that has a mutated epidermal growth factor receptor (EGFR) or or displaced anaplastic lymphoma receptor tyrosine kinase (ALK) or ROS… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-small Cell Lung Cancer Metastatic, Targetable Oncogenes (EGFR, ALK, ROS1)
- What is being tested?
- SBRT with protons or photons
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2014to 25 Oct 2023
- Phase
- Phase 2
- 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
- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with any actionable mutation or translocation in EGFR, ALK, or ROS1
- Stage IV disease (AJCC Staging system 7th edition)
- Within 6 months of initiating their first TKI treatment regimen
- Stable or responding systemic disease to TKI (no evidence of progression) on the most recent staging studies. The complete extent of the current residual systemic disease must be deemed amenable to SBRT as per review of imaging studies by a radiation oncologist, based on the following criteria:
- Lung: 1-3 lesions (including the primary) of maximum size 5 cm in longest diameter. A minimum size 1 cm in the longest diameter is recommended. (Patients with a malignant pleural effusion prior to the start of TKI therapy will be considered eligible for SBRT if there is complete radiographic resolution of the effusion while on systemic therapy);
- Spine: Bone lesions must be limited to the spine. A maximum of 2 spinal metastases will be considered for SBRT, with each site spanning 1-3 vertebral bodies. A minimum size of 1 cm in longest diameter is recommended. SBRT may target sclerotic lesions that persist following TKI therapy;
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- GI: 1-4 liver metastases of maximum size 5 cm in longest diameter and/or 1-2 adrenal metastases of maximum 4 cm size in longest diameter. A minimum size of 1 cm in longest diameter is recommended.
- In addition:
- CNS: 1-4 brain metastases of maximum size 3cm in longest diameter. However, these should be treated with standard-of-care SRS and will not be defined as target lesions for purposes of this protocol.
- A maximum number of 5 target lesions outside the brain, excluding the lung primary, is recommended to ensure that enrollment is limited to patients with low-burden disease and that treatments can be delivered within the specified time frame.
- History of prior radiation therapy to brain or skeleton is allowed, but should have occurred > 2 months from enrollment.
- Age at least 18 years.
- Life expectancy of greater than 6 months.
- ECOG performance status ≤ 2.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A negative serum or urine pregnancy test within 2 weeks of registration for women of childbearing potential is required.
- Ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Residual hilar or mediastinal lymph node disease (size > 1cm in short-axis diameter on CT). Non-malignant etiologies for enlarged lymph nodes may be evaluated per standard clinical practice.
- Participants who have received prior radiation therapy to anatomical sites other than brain or skeleton.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who are pacemaker or defibrillator-dependent as these devices may not be operated concurrently with delivery of proton beam radiation.
- Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
Official title: A Phase II Trial of Integrating Stereotactic Body Radiation Therapy With Selective Targeted Therapy in Stage IV Oncogene-driven Non-Small Cell Lung Cancer
This research study is studying a type of radiation therapy called Stereotactic Body Radiation Therapy (SBRT) as a possible treatment for stage IV non-small cell lung cancer (NSCLC) that has a mutated epidermal growth factor receptor (EGFR) or or displaced anaplastic lymphoma receptor tyrosine kinase (ALK) or ROS proto-oncogene 1 (ROS1) gene (= oncogene-driven NSCLC) and for which the subject has been receiving treatment with a targeted biological agent such as erlotinib, crizotinib, or other drugs.
Read the detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. The investigational intervention in this study is SBRT with proton or photon radiation (explained below). "Investigational" means that the intervention is being studied. SBRT and proton radiation therapy are FDA approved radiation delivery systems. However, using it as a treatment for stage IV NSCLC is still investigational.
SBRT is a specialized, technologically advanced type of external beam radiation therapy that pinpoints high doses of radiation directly on the cancer. Because of high precision, these treatments spare healthy tissue and are associated with fewer side effects. SBRT is very different from conventional therapy where radiation is delivered in small doses given daily over the course of several weeks. For SBRT, the total dose of radiation is typically administered in 4-5 daily sessions. SBRT can be delivered with standard, so called photon radiation, or proton beam. Neither of these two types of radiation is generally superior over the other. There are technical differences between these two, and depending on tumor location, size, shape, and other factors, the investigators will decide which type of radiation to use for which treatment.
After the screening procedures confirm you are eligible to participate in the research study:
- Each participant will receive stereotactic treatment course (SBRT with protons or photons) to the area of their tumor.
- Being tested
- SBRT with protons or photons
- Keywords
- Non-small cell lung cancer, Metastatic, EGFR, ALK, ROS1, Stereotactic Body Radiation Therapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRT with protons or photonsRadiation
Also called Stereotactic body radiation therapy
| Study group | Role | What they receive |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | Experimental | * SBRT dosage determined by treating physician
* Patients will continue to receive standard of care (SOC) tyrosine kinase inhibitors (TKI) in the intervals between SBRT courses, as well as after the completion of SBRT
* If there is more than one active site of cancer, additional site(s) will be treated with stereotactic treatment courses. The total duration of SBRT courses (from the first day of any SBRT course to the last day of any SBRT course) will not exceed 4 months. Receives: Radiation: SBRT with protons or photons |
What is being measured
The primary outcome is the main question the study is designed to answer.
1-year Frequency of Distant Failures (DF) After Stereotactic Body Radiation Therapy (SBRT)
Distant failures (DF) are defined as metastases outside areas that originally contained disease. The 1-year frequency of DF is defined as the percentage of patients that experienced a DF, respectively, over the course of one year.
Measured: 1 year
Secondary outcomes (5)
Percentage of Participants With Grade 3 or Higher Toxicities Related to Stereotactic Body Radiation Therapy (SBRT)
Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE v4.0). Treatment-related toxicities are defined as adverse events assessed as related to SBRT.
Measured: Up to 8.4 years
Median Progression Free Survival
Progression free survival is defined as the duration of time from the start of standard of care TKI (tyrosine kinase inhibitor) therapy until objective progressive disease or death. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: Up to 7.65 years
Median Overall Survival
Overall survival is defined as the duration of time from the start of documented tyrosine kinase inhibitor (TKI) therapy to the time of death.
Measured: Up to 8.4 years
2-year Overall Survival
Overall survival is defined as the duration of time from the start of documented tyrosine kinase inhibitor (TKI) therapy to the time of death. The 2-year overall survival is defined as the percentage of participants who were alive 2 years after the start of documented tyrosine kinase inhibitor (TKI) therapy.
Measured: 2 years
2-year Local Failure (LF) of Lesions Treated With Stereotactic Body Radiation Therapy (SBRT)
Local failure is defined as progressive disease in target lesions treated with SBRT. The 2-year LF rate is the percentage of participants who experienced local failure within 2 years of completing SBRT.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2014 (estimated)
- Study startDec 2014
- Primary completion10 Nov 2021
- Study completion25 Oct 2023
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 Non-small Cell Lung Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Henning Willers, M.D., Massachusetts General Hospital
- Investigators
- Henning Willers, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02314364
- Sponsor's protocol ID
- 14-370
- Status last verified
- Sep 2025
- First submitted
- 20 Nov 2014
- Last updated
- 16 Dec 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Integrating Stereotactic Body Radiation Therapy With Selective Targeted Therapy in Stage IV Oncogene-driven Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02314364
- Acronym / sponsor ID
- 14-370
- Keywords
- Non-small cell lung cancer, Metastatic, EGFR, ALK, ROS1, Stereotactic Body Radiation Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2014
- Primary completion
- 10 Nov 2021 (actual)
- Study completion
- 25 Oct 2023 (actual)
- First posted
- 11 Dec 2014 (estimated)
- Results
- Posted 4 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This research study is studying a type of radiation therapy called Stereotactic Body Radiation Therapy (SBRT) as a possible treatment for stage IV non-small cell lung cancer (NSCLC) that has a mutated epidermal growth factor receptor (EGFR) or or displaced anaplastic lymphoma receptor tyrosine kinase (ALK) or ROS proto-oncogene 1 (ROS1) gene (= oncogene-driven NSCLC) and for which the subject has been receiving treatment with a targeted biological agent such as erlotinib, crizotinib, or other drugs.
Detailed description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. The investigational intervention in this study is SBRT with proton or photon radiation (explained below). "Investigational" means that the intervention is being studied. SBRT and proton radiation therapy are FDA approved radiation delivery systems. However, using it as a treatment for stage IV NSCLC is still investigational.
SBRT is a specialized, technologically advanced type of external beam radiation therapy that pinpoints high doses of radiation directly on the cancer. Because of high precision, these treatments spare healthy tissue and are associated with fewer side effects. SBRT is very different from conventional therapy where radiation is delivered in small doses given daily over the course of several weeks. For SBRT, the total dose of radiation is typically administered in 4-5 daily sessions. SBRT can be delivered with standard, so called photon radiation, or proton beam. Neither of these two types of radiation is generally superior over the other. There are technical differences between these two, and depending on tumor location, size, shape, and other factors, the investigators will decide which type of radiation to use for which treatment.
After the screening procedures confirm you are eligible to participate in the research study:
- Each participant will receive stereotactic treatment course (SBRT with protons or photons) to the area of their tumor.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Stereotactic body radiation therapy (SBRT) with protons or photons | Experimental | Radiation: SBRT with protons or photons* SBRT dosage determined by treating physician * Patients will continue to receive standard of care (SOC) tyrosine kinase inhibitors (TKI) in the intervals between SBRT courses, as well as after the completion of SBRT * If there is more than one active site of cancer, additional site(s) will be treated with stereotactic treatment courses. The total duration of SBRT courses (from the first day of any SBRT course to the last day of any SBRT course) will not exceed 4 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with any actionable mutation or translocation in EGFR, ALK, or ROS1
- Stage IV disease (AJCC Staging system 7th edition)
- Within 6 months of initiating their first TKI treatment regimen
- Stable or responding systemic disease to TKI (no evidence of progression) on the most recent staging studies. The complete extent of the current residual systemic disease must be deemed amenable to SBRT as per review of imaging studies by a radiation oncologist, based on the following criteria:
- CNS: 1-4 brain metastases of maximum size 3cm in longest diameter. However, these should be treated with standard-of-care SRS and will not be defined as target lesions for purposes of this protocol.
Key exclusion criteria (5 listed)
- Residual hilar or mediastinal lymph node disease (size > 1cm in short-axis diameter on CT). Non-malignant etiologies for enlarged lymph nodes may be evaluated per standard clinical practice.
- Participants who have received prior radiation therapy to anatomical sites other than brain or skeleton.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Patients who are pacemaker or defibrillator-dependent as these devices may not be operated concurrently with delivery of proton beam radiation.
- Pregnant or lactating women, as treatment involves unforeseeable risks to the embryo or fetus.
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 |
|---|---|---|
| SBRT with protons or photonsAlso: Stereotactic body radiation therapy | Radiation | Stereotactic body radiation therapy (SBRT) with protons or photons |
Primary outcome
1-year Frequency of Distant Failures (DF) After Stereotactic Body Radiation Therapy (SBRT)
Time frame: 1 year
Distant failures (DF) are defined as metastases outside areas that originally contained disease. The 1-year frequency of DF is defined as the percentage of patients that experienced a DF, respectively, over the course of one year.
5 secondary outcomes
Percentage of Participants With Grade 3 or Higher Toxicities Related to Stereotactic Body Radiation Therapy (SBRT)
Time frame: Up to 8.4 years
Median Progression Free Survival
Time frame: Up to 7.65 years
Median Overall Survival
Time frame: Up to 8.4 years
2-year Overall Survival
Time frame: 2 years
2-year Local Failure (LF) of Lesions Treated With Stereotactic Body Radiation Therapy (SBRT)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 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.
Henning Willers, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SBRT with protons or photons in people with Non-small Cell Lung Cancer Metastatic and Targetable Oncogenes (EGFR, ALK, ROS1), run by Massachusetts General Hospital 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 16 inclusion and 5 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 16 Dec 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 4 Mar 2024). 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?
1-year Frequency of Distant Failures (DF) After Stereotactic Body Radiation Therapy (SBRT) (time frame: 1 year). 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 16 Dec 2025.