A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

NCT ID: NCT03368625

Last Updated: 2025-02-20

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-19
• Study Completion Date: 2027-12-01

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).

Detailed Description

Recently, a novel treatment strategy for large brain metastases was described whereby lesions appropriate for resection were treated with a single fraction of SRS pre-operatively. In a retrospective analysis, of 51 lesions with a median tumor size of 3 cm, 1-year LC was 86%. This neoadjuvant approach resulted in lower rates of leptomeningeal failure (3 vs. 17%) and symptomatic radiation toxicity (1.5 vs. 14.6 %) compared to a comparative cohort of lesions treated with post-operative cavity boost SRS (POCBS).

Based on promising results, we believe that a prospective trial to establish the value of neoadjuvant SRS (NaSRS) for the treatment of BM appropriate for resection is warranted.

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Neoadjuvant SRS

Group Type: OTHER

Stereotactic Radiosurgery

Intervention Type: RADIATION

Stereotactic Radiosurgery before surgical resection of brain mets.

Interventions

Stereotactic Radiosurgery

Stereotactic Radiosurgery before surgical resection of brain mets.

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Shultz, MD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

University Health Network

Toronto, Ontario, Canada

Site Status: RECRUITING

Charité Universitätsmedizin Berlin, Campus Virchow Klinikum

Berlin, , Germany

Site Status: RECRUITING

Countries

Canada; Germany

Central Contacts

David Shultz, M.D.

Role: CONTACT

david.shultz@rmp.uhn.ca

416-946-4501 ext. 6899

Facility Contacts

David Shultz, MD

Role: primary

Güliz Acker, PD Dr. med

Role: primary

gueliz.acker@charite.de

+49 30 450 660357 ext. 491702291071

Sylvia Blass

Role: backup

sylvia.blass@charite.de

+49 30 450 527318

References

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.

Reference Type: DERIVED

PMID: 40227031 (View on PubMed)

Other Identifiers

17-5689

Identifier Type: -

Identifier Source: org_study_id