Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases

Stereotactic Radiation in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases: A Single Arm, Phase II Trial

This research study is studying stereotactic radiation (focused/pinpoint radiation that targets each individual tumor but not the surrounding brain) instead of whole-brain radiation (radiation targeting the entire brain) as a possible treatment for patients with small cell lung cancer and 1-10 brain metastases.

The intervention involved in this study is:

-Stereotactic (focused, pinpoint) radiation

Study Overview

• Status: Active, not recruiting
• Conditions: Small Cell Lung Cancer; Brain Metastases
• Intervention / Treatment: Radiation: Stereotactic Radiation

Detailed Description

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational treatment, in this case stereotactic radiation, to learn whether this treatment works in treating a specific disease. "Investigational" means that the treatment is being studied.

In patients with a limited number of brain metastases (spread of a cancer that started outside of the brain to the brain itself) the standard radiation option is stereotactic radiation, which involves using a high dose of radiation that only targets the specific metastases that are visible on imaging of the brain, not the whole brain itself. However, studies evaluating the role of stereotactic radiation to treat brain metastases generally excluded patients with small cell lung cancer. Therefore, among patients with small cell lung cancer and brain metastases, the typical treatment that has been offered is whole brain radiation. However, whole brain radiation has deleterious associated side effects including significant fatigue and permanent memory/attention problems. The investigators are studying whether stereotactic radiation can be effectively utilized for patients with small cell lung cancer and brain metastases in order to avoid such side effects.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participants must have a biopsy-proven tumor consistent with small cell lung cancer and intracranial lesions radiographically consistent with or pathologically proven to be brain metastases. Patients who have undergone prior systemic therapy are eligible. Patients who have undergone resection of one or more brain metastases but who have not yet started adjuvant radiotherapy are eligible for the study.
• 1-10 definitive intracranial lesions must be present on MRI of the brain.
• Age >=18 years at diagnosis of brain metastases.

Exclusion Criteria:

• Participants who have undergone prior radiation for brain metastases.
• Participants who have received prophylactic cranial radiation for prevention of brain metastases
• Participants who cannot receive gadolinium
• Participants with stage IV-V chronic kidney disease or end stage renal disease
• Participants with widespread, definitive leptomeningeal disease
• Participants with a maximum tumor diameter exceeding 5 cm (if not resected)
• Participants with >6 definitive lesions consistent with brain metastases
• Participants with inadequate mental capacity to complete quality of life questionnaires

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 Radiation; Stereotactic radiation will begin within 14 days of the MRI used for radiation planning; Lesions <2 cm in maximum diameter will be treated with stereotactic radiosurgery, generally 20 Gy in 1 fraction; Lesions between 2.0 and 3.0 cm in maximum diameter will generally be treated to 18 Gy in 1 fraction; Lesions >3 cm will be generally be treated with stereotactic radiotherapy to 30 Gy in 5 fractions

Radiation: Stereotactic Radiation; Stereotactic radiation involves using a high dose of radiation that only targets the specific metastases

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neurologic Mortality	Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease).	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause Mortality	Death from any cause cumulative incidence estimate assessed at 1 year and 2 year	Until death or loss to follow up, up to 24 months
Quality of Life as Assessed by Patient Questionnaire	Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT)	Until death or loss to follow up, up to 24 months
Neurocognitive Function: Verbal Learning and Memory	Hopkins Verbal Learning Test -Revised (HVLT-R). Scores are transformed into Z scores.	12 months
Neurocognitive Function: Visual Attention and Task Switching	Trail Making Test Part A and B (TMT). Scores are transformed into Z scores.	12 months
Neurocognitive Function: Verbal Fluency	Controlled Oral Word Association Test (COWAT). Scores are transformed into Z scores.	12 months
Neurocognitive Function: Cognitive Impairment	Mini Mental Status Examination (MMSE). Scored 0 to 30. Higher scores indicate better cognitive function	12 months
Ability to Complete Activities of Daily Living	Questionnaire - EQ-5D. A patient reported quality of life questionnaire	Until death or loss to follow up, up to 24 months
Performance Status	Karnofsky performance status. Scale ranges from 0 to 100, with higher scores indicating better function.	Until death or loss to follow up, up to 24 months
One and Two Year Incidence of New Brain Metastases	1 and 2 year estimates of first appearance of new brain metastases (on radiographic assessment)	Until death or loss to follow up, up to 24 months
Incidence of Existing Brain Metastases	Per patient radiographic assessment of first event of local recurrence in the brain metastases treated with radiation on trial. One- and 2-Year estimates.	Until death or loss to follow up, up to 24 months
Incidence of Development of Radiographic Radiation Necrosis	Per patient radiographic assessment of first event of radiation necrosis in the brain metastases treated with radiation on trial. One- and 2-Year cumulative incidence estimates.	Until death or loss to follow up, up to 24 months
Incidence of Development of Leptomeningeal Disease	Per patient radiographic assessment of first event of leptomeningeal disease. One- and 2-Year estimates.	Until death or loss to follow up, up to 24 months
Incidence of Salvage Craniotomy	Per patient clinical assessment of first use of neurosurgical resection / craniotomy as salvage therapy in metastases treated with radiation on trial. One- and 2-Year estimates.	Until death or loss to follow up, up to 24 months
Incidence of Additional CNS-directed Radiotherapeutic Treatments (Stereotactic Radiation) After the Initial Course	Per patient clinical assessment of first use of salvage brain-directed stereotactic radiation. 1- and 2-Year estimates.	Until death or loss to follow up, up to 24 months
Incidence of Seizures	Per patient clinical assessment of first post-treatment seizure as assessed during routine study visits and via medical record review. 1 and 2-Year estimates.	Until death or loss to follow up, up to 24 months
Incidence of Symptomatic Radiation Necrosis	Per patient assessment of first event of symptomatic radiation necrosis in the brain metastases treated with radiation on trial. 1- and 2-Year estimates.	Until death or loss to follow up, up to 24 months
Incidence of Neurologic Death at 2 Years	Clinical parameter to be assessed via review of study visits and medical records indicating cause of death (neurologic versus systemic progressive disease).	2-years
Incidence of Additional CNS-directed Radiotherapeutic Treatments (Whole Brain Radiation) After the Initial Course	Per patient clinical assessment of first use of salvage whole brain radiation. One- and 2-Year estimates.	Until death or loss to follow up, up to 24 months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Dana-Farber Cancer Institute
• Investigators: Principal Investigator: Ayal A Aizer, MD, Brigham and Women's Hospital

Publications and helpful links

General Publications

• Aizer AA, Tanguturi SK, Shi DD, Catalano PJ, Shin KY, Ricca I, Johnson M, Benham G, Kozono DE, Mak RH, Hertan L, Chipidza F, Krishnan M, Pashtan I, Peng L, Qian JM, Shiloh RY, Cagney DN, Sands J, Brown PD, Wen PY, Haas-Kogan DA, Rahman R. Stereotactic Radiosurgery in Patients With Small Cell Lung Cancer and 1-10 Brain Metastases: A Multi-Institutional, Phase II, Prospective Clinical Trial. J Clin Oncol. 2025 Sep 20;43(27):2986-2997. doi: 10.1200/JCO-25-00056. Epub 2025 Jul 11.

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2018
• Primary Completion (Actual): April 10, 2024
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: December 21, 2017
• First Submitted That Met QC Criteria: December 29, 2017
• First Posted (Actual): January 5, 2018

Study Record Updates

• Last Update Posted (Actual): July 14, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Quality of life; Lung cancer; Neurocognitive; Stereotactic; Brain Metastases; Small Cell Lung Cancer; SRS; Radiation; Neurocognition; Stereotactic radiosurgery; Brain metastasis; Stereotactic radiation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Nervous System Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Brain Neoplasms; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: 17-550

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No