A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

Brain Metastases Clinical Trial

— NASRS  

Official title:

A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03368625
• Other study ID #: 17-5689
• Status: Recruiting
• Phase: N/A
• Start date: March 19, 2018
• Est. completion date: December 1, 2024

Study information

• Verified date: October 2023
• Source: University Health Network, Toronto
• Contact: David Shultz, M.D.
• Phone: 416-946-4501
• Email: david.shultz[@]rmp.uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Metastases
• Brain Neoplasms
• Neoplasm Metastasis

Intervention

Radiation:
• Stereotactic Radiosurgery
Stereotactic Radiosurgery before surgical resection of brain mets.

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario
Germany	Charité Universitätsmedizin Berlin, Campus Virchow Klinikum	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Countries where clinical trial is conducted

Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radiation toxicity	The rate at 1 year of symptomatic (=grade 2) radiation toxicity	1 year
Secondary	local control	1-year local control (PR+CR) of the index lesion resulting from NaSRS	1 year
Secondary	leptomeningeal disease	1-year rates of leptomeningeal disease	1 year
Secondary	Survival	Median survival	5 years
Secondary	progression-free survival		2 years
Secondary	overall survival		2 years