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A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases (NASRS)

Primary Purpose

Brain Metastases

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
Stereotactic Radiosurgery
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain Metastases focused on measuring Stereotactic Radiosurgery, Radiation, Surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University Health NetworkRecruiting
  • Charité Universitätsmedizin Berlin, Campus Virchow KlinikumRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Arm 1

Arm Description

Neoadjuvant SRS

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

local control
1-year local control (PR+CR) of the index lesion resulting from NaSRS
leptomeningeal disease
1-year rates of leptomeningeal disease
Survival
Median survival
progression-free survival
overall survival

Full Information

First Posted
December 4, 2017
Last Updated
October 9, 2023
Sponsor
University Health Network, Toronto
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1. Study Identification

Unique Protocol Identification Number
NCT03368625
Brief Title
A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases
Acronym
NASRS
Official Title
A Phase II Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 19, 2018 (Actual)
Primary Completion Date
December 1, 2024 (Anticipated)
Study Completion Date
December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Brain Metastases
Keywords
Stereotactic Radiosurgery, Radiation, Surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Patients with resectable brain mets will receive neoadjuvant stereotactic radiosurgery prior to surgical resection.
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Other
Arm Description
Neoadjuvant SRS
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Radiosurgery
Intervention Description
Stereotactic Radiosurgery before surgical resection of brain mets.
Primary Outcome Measure Information:
Title
Radiation toxicity
Description
The rate at 1 year of symptomatic (≥grade 2) radiation toxicity
Time Frame
1 year
Secondary Outcome Measure Information:
Title
local control
Description
1-year local control (PR+CR) of the index lesion resulting from NaSRS
Time Frame
1 year
Title
leptomeningeal disease
Description
1-year rates of leptomeningeal disease
Time Frame
1 year
Title
Survival
Description
Median survival
Time Frame
5 years
Title
progression-free survival
Time Frame
2 years
Title
overall survival
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
David Shultz, M.D.
Phone
416-946-4501
Ext
6899
Email
david.shultz@rmp.uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Shultz, MD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
L4W4C2
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David Shultz, MD
Facility Name
Charité Universitätsmedizin Berlin, Campus Virchow Klinikum
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Güliz Acker, PD Dr. med
Phone
+49 30 450 660357
Ext
491702291071
Email
gueliz.acker@charite.de
First Name & Middle Initial & Last Name & Degree
Sylvia Blass
Phone
+49 30 450 527318
Email
sylvia.blass@charite.de
First Name & Middle Initial & Last Name & Degree
Güliz Acker, PD Dr. med
First Name & Middle Initial & Last Name & Degree
Carolin Senger, Dr. med

12. IPD Sharing Statement

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A Study of Neoadjuvant Stereotactic Radiosurgery for Large Brain Metastases

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