Hippocampal Sparing Whole Brain Radiation Versus Stereotactic Radiation in Patients With 5-20 Brain Metastases: A Phase III, Randomized Trial

NCT03075072 | Active Not Recruiting Results DMC FDA Device

• 1 other identifier: 16-305
• Study Type: interventional
• Target: 196
• Locations: 1 country
• Sites: 2

Brief Summary

This research study is studying two different types of radiation as treatment for brain metastases (tumors in the brain that spread from a cancer that originated elsewhere in the body)

Conditions

Brain Metastases

Keywords

Brain metastases; Brain metastasis; Lung cancer; Melanoma; Breast cancer; Kidney cancer; Renal cell carcinoma; Stereotactic radiation; Stereotactic radiosurgery; SRS; Stereotactic; Whole brain radiation; WBRT; Hippocampal avoidance; Hippocampal sparing; Hippocampal; Hippocampus; Radiation; Quality of Life; Neurocognitive; Neurocognition; Survival; Salvage; MDASI; Chemotherapy; Recurrence

Outcome Measures

Primary Outcomes (1)

• Change in MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT) Score

  Questionnaire - MD Anderson Symptom Inventory - Brain Tumor (MDASI-BT). Results reflect patient-reported symptoms. Here they are presented as a mean change: the difference in the weighted mean of symptom severity and interference scores at baseline versus at 6 months. The difference between these scores is the mean change reported below. The MD Anderson Symptom Inventory has a scale of 0-10, 0 being not present and 10 being as bad as the patient could imagine. The calculated score change has a range of -10 to 10; -10 being the best. Change in score is calculated as the composite weighted means of symptom severity and interference at 6 months minus the composite weighted means of symptom severity and interference at baseline.

  Baseline and 6 months post-Baseline

Secondary Outcomes (31)

• Overall Survival

  Through study completion, an average of 1 year

• 12 Month Cumulative Incidence of Neurologic Death

  Through study completion, an average of 1 year

• 12 Month Cumulative Incidence of New Brain Metastases

  Through study completion, an average of 1 year

• 12 Month Cumulative Incidence of Local Recurrence of Treated Brain Tumor(s)

  Through study completion, an average of 1 year

• 12 Month Cumulative Incidence of Progressive Intracranial Disease

  Through study completion, an average of 1 year

Study Arms (2)

Whole Brain Radiation

ACTIVE COMPARATOR

* MRI will be performed prior to radiation is administered * A hippocampal sparing approach will be used when possible * Dose will be 30 Gy in 10 fractions

Radiation: Whole brain radiation

Stereotactic Radiation (SRS)

EXPERIMENTAL

* MRI will be performed prior to radiation is administered * Radiation will be given in 1-5 fractions (dose depends on the size of the tumor that will be treated)

Radiation: Stereotactic radiation (SRS)

Interventions

Whole brain radiation RADIATION

Treatment of the whole brain with radiation. When possible the hippocampus will be spared from radiation.

Whole Brain Radiation

Stereotactic radiation (SRS) RADIATION

Focused radiation to each individual brain metastasis without treatment of the remainder of the brain.

Stereotactic Radiation (SRS)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a biopsy proven solid malignancy with untreated (by radiation) intracranial lesions radiographically consistent with or pathologically proven to be brain metastases. Patients who have undergone prior systemic therapy are eligible
• Five-twenty intracranial lesions must be present on MRI of the brain
• Age 18-80 years at diagnosis of brain metastases
• Karnofsky performance status of at least 70

You may not qualify if:

• Participants who have undergone prior radiation for brain metastases.
• Patients who have undergone resection of one or more brain metastases but who have not yet started adjuvant radiotherapy are eligible for the study
• Participants who cannot undergo a brain MRI
• Participants who cannot receive gadolinium (MRI contrast)
• Participants with stage IV-V chronic kidney disease or end stage renal disease
• Participants with widespread, definitive leptomeningeal disease
• Participants with small cell lung cancer, lymphoma, or myeloma
• Participants with a maximum tumor diameter exceeding 5 cm (if not resected)

Sponsors & Collaborators

• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: lead

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02116, United States

Location

Related Publications (4)

• Ayal Aizer et al. Stereotactic radiation versus hippocampal avoidance whole brain radiation in patients with 5-20 brain metastases: A multicenter, phase 3 randomized trial.. J Clin Oncol 43, 2011-2011(2025). DOI:10.1200/JCO.2025.43.16_suppl.2011

  RESULT

• Aizer A et al. Multicenter, Phase 3 Randomized Trial of Stereotactic Radiation vs. Hippocampal Avoidance Whole Brain Radiation in Patients with 5-20 Brain Metastases: Recurrence, Salvage Therapy, and Mortality Endpoints International Journal of Radiation Oncology, Biology, Physics, 123, S33-S34

  RESULT

• Michael Parsons, Kee-Young Shin, Jennifer Nosker, Shyam Tanguturi, Paul Catalano, Daphne Haas-Kogan, Jaroslaw Hepel, Marciana Johnson, Grant Benham, Ivy Ricca, Rifaquatn Rahma, Ayal Aizer, NCOG-20. Stereotactic radiation versus hippocampal avoidant whole brain radiation in patients with 5-20 brain metastases: Cognitive outcomes of 12-month survivors, Neuro-Oncology, Volume 27, Issue Supplement_5, November 2025, Pages v325-v326, https://doi.org/10.1093/neuonc/noaf201.1287

  RESULT

• Aizer AA, Shin KY, Catalano PJ, Ricca I, Johnson M, Benham G, Roper K, Spicer B, Mann E, Nosker J, Parsons MW, Mendu ML, Hepel J, Chipidza F, Krishnan M, Shi DD, Lamba N, Pashtan I, Peng L, Alexander B, Brown PD, Wen PY, Haas-Kogan DA, Rahman R, Tanguturi S. Treatment for Brain Metastases With Stereotactic Radiation vs Hippocampal-Avoidance Whole Brain Radiation: A Randomized Clinical Trial. JAMA. 2026 Apr 7;335(13):1127-1136. doi: 10.1001/jama.2026.0076.

  PMID: 41712219 RESULT

MeSH Terms

Conditions

Brain Neoplasms; Lung Neoplasms; Melanoma; Breast Neoplasms; Kidney Neoplasms; Carcinoma, Renal Cell; Recurrence

Interventions

Radiosurgery; Spermine Synthase

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases; Breast Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Alkyl and Aryl Transferases; Transferases; Enzymes; Enzymes and Coenzymes

Limitations and Caveats

Per manuscript

Results Point of Contact

• Title: Ayal Aizer, MD, MHS
• Organization: Brigham and Women's Hospital

aaaizer@mgb.org

(617) 732-7560

Study Officials

• Ayal Aizer, MD MHS

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 1, 2017
• First Posted: March 9, 2017
• Study Start: April 10, 2017
• Primary Completion: November 7, 2024
• Study Completion (Estimated): September 30, 2027
• Last Updated: September 29, 2026
• Results First Posted: September 29, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)