A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

NCT03368625 | Completed

• 1 other identifier: 17-5689
• Study Type: interventional
• Target: 30
• Locations: 2 countries
• Sites: 2

Brief Summary

This study will be a non-randomized phase II trial for patients with one to six brain metastases, at least one of which is appropriate for surgical resection. Upon registration, patients will be assigned to receive neo-adjuvant stereotactic radiosurgery (NASRS).

Conditions

Brain Metastases

Keywords

Stereotactic Radiosurgery; Radiation; Surgery

Outcome Measures

Primary Outcomes (1)

• Radiation toxicity

  The rate at 1 year of symptomatic (≥grade 2) radiation toxicity

  1 year

Secondary Outcomes (5)

• local control

  1 year

• leptomeningeal disease

  1 year

• Survival

  5 years

• progression-free survival

  2 years

• overall survival

  2 years

Study Arms (1)

Arm 1

OTHER

Neoadjuvant SRS

Radiation: Stereotactic Radiosurgery

Interventions

Stereotactic Radiosurgery RADIATION

Stereotactic Radiosurgery before surgical resection of brain mets.

Arm 1

Eligibility Criteria

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

You may qualify if:

• Lymphoma, small cell carcinoma, and seminoma are excluded
• A lesion appropriate for resection, not previously treated with SRS. Lesions should be \> 2 cm and \< 4 cm in largest dimension, and require resection ( e.g. due to mass effect or to obtain a tissue diagnosis). Index lesions will be treated with SRS and surgery, as outlined in the treatment section of the protocol.
• Seen by a neurosurgeon or radiation oncologist and judged to be appropriate for participation in this study, including the ability to tolerate NaSRS, e.g., the ability to lie flat in a stereotactic head frame.
• Any unresected lesions or lesions for which there is no planned immediate resection (non index lesions) must measure \< 3.0 cm in maximal extent on the contrasted MRI or CT brain scan obtained ≤ 35 days prior to pre-registration. Unresected lesions will be treated with SRS as outlined in the treatment section of the protocol. .
• ECOG ≤ 2
• MRI confirmed 1-6 lesions, one of which is the index lesion. Each non-index lesion (up to 5) must measure ≤ 3.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection.
• Note: The pre-registration MRI may be obtained ≤ 35 days prior to enrolment.

You may not qualify if:

• Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
• pregnancy
• Prior cranial radiotherapy targeting the index lesion, or any prior WBRT.
• Inability to complete a MRI with contrast of the head, or a known allergy to gadolinium.
• Cytotoxic Chemotherapy within 7 days prior to SRS (molecularly targeted therapies , including immune-modulatory drugs, can be given within seven days of SRS at the discretion of the treating physician)
• Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor
• Imaging Findings:
• Widespread definitive leptomeningeal metastasis.
• A brain metastasis that is located ≤ 2 mm of the optic chiasm
• Evidence of midline shift
• Fourth ventricular narrowing, concerning for hydrocephalus

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (2)

University Health Network

Toronto, Ontario, L4W4C2, Canada

Location

Charité Universitätsmedizin Berlin, Campus Virchow Klinikum

Berlin, 13353, Germany

Location

Related Publications (1)

• Higazy R, Li D, Lau R, Millar BA, Laperriere N, Berlin A, Conrad T, Gutierrez-Valencia E, Zadeh G, Bernstein M, Kalyvas A, Spears J, Zips D, Vajkoczy P, Senger C, Acker G, Kongkham P, Shultz DB. Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases: An International, Multicenter, Single-Arm Phase II Trial. Neurosurgery. 2025 Apr 14;97(4):793-800. doi: 10.1227/neu.0000000000003451.

  PMID: 40227031 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Radiosurgery

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• David Shultz, MD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients with resectable brain mets will receive neoadjuvant stereotactic radiosurgery prior to surgical resection.

Study Record Dates

• First Submitted: December 4, 2017
• First Posted: December 11, 2017
• Study Start: March 19, 2018
• Primary Completion: October 10, 2025
• Study Completion: October 10, 2025
• Last Updated: March 4, 2026

Record last verified: 2026-03

Locations

DE (1); CA (1)