A Trial of Integrating SBRT With Targeted Therapy in Stage IV Oncogene-driven NSCLC

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.

Study Overview

• Status: Completed
• Conditions: Non-small Cell Lung Cancer Metastatic; Targetable Oncogenes (EGFR, ALK, ROS1)
• Intervention / Treatment: Radiation: SBRT with protons or photons

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 Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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;
  • 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Stereotactic body radiation therapy (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.

Radiation: SBRT with protons or photons; Other Names: Stereotactic body radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	2 years
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.	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.	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.	Up to 8.4 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Henning Willers, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): November 10, 2021
• Study Completion (Actual): October 25, 2023

Study Registration Dates

• First Submitted: November 20, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (Estimated): December 11, 2014

Study Record Updates

• Last Update Posted (Estimated): December 16, 2025
• Last Update Submitted That Met QC Criteria: November 29, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Non-small cell lung cancer; EGFR; Metastatic; Stereotactic Body Radiation Therapy; ROS1; ALK
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Physical Phenomena; Inorganic Chemicals; Elements; Ions; Electrolytes; Electromagnetic Phenomena; Magnetic Phenomena; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Electromagnetic Radiation; Radiation; Gases; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing; Cations, Monovalent; Cations; Hydrogen; Nucleons; Radiosurgery; Photons; Protons
• Other Study ID Numbers: 14-370