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

NCT02314364 | Completed Phase 2 Results DMC

• 1 other identifier: 14-370
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Non-small Cell Lung Cancer Metastatic; Targetable Oncogenes (EGFR, ALK, ROS1)

Keywords

Non-small cell lung cancer; Metastatic; EGFR; ALK; ROS1; Stereotactic Body Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Percentage of Participants With Grade 3 or Higher Toxicities Related to Stereotactic Body Radiation Therapy (SBRT)

  Up to 8.4 years

• Median Progression Free Survival

  Up to 7.65 years

• Median Overall Survival

  Up to 8.4 years

• 2-year Overall Survival

  2 years

• 2-year Local Failure (LF) of Lesions Treated With Stereotactic Body Radiation Therapy (SBRT)

  2 years

Study Arms (1)

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.

Radiation: SBRT with protons or photons

Interventions

SBRT with protons or photons RADIATION

Also known as: Stereotactic body radiation therapy

Stereotactic body radiation therapy (SBRT) with protons or photons

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Radiosurgery; Protons; Photons

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Cations, Monovalent; Cations; Ions; Electrolytes; Inorganic Chemicals; Hydrogen; Elements; Gases; Nucleons; Elementary Particles; Physical Phenomena; Light; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Optical Phenomena; Radiation; Radiation, Nonionizing

Results Point of Contact

• Title: Henning Willers, MD
• Organization: Massachusetts General Hospital

hwillers@mgh.harvard.edu

617-726-5184

Study Officials

• Henning Willers, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 20, 2014
• First Posted: December 11, 2014
• Study Start: December 1, 2014
• Primary Completion: November 10, 2021
• Study Completion: October 25, 2023
• Last Updated: December 16, 2025
• Results First Posted: March 4, 2024

Record last verified: 2025-09

Locations

US (1)