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Single vs Multi-fraction SRS Patients on Immunotherapy (MIGRAINE)

Primary Purpose

Brain Cancer, Brain Metastases

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Radiosurgery Single Treatment

Radiosurgery Three Treatments

About this trial

This is an interventional treatment trial for Brain Cancer

Eligibility Criteria

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

Inclusion Criteria:

i. Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more.

ii. Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-10 newly diagnosed intraparenchymal brain metastases.

iii. Well-circumscribed, measureable intraparenchymal brain metastasis(s) with maximum tumor diameter ≤3.0 cm. If multiple metastases are present, the other(s) must not exceed 3.0 cm in maximum diameter. At least one metastasis must be ≥ 0.5 cm in maximum diameter to be considered measurable disease.

iv. Negative urine or serum pregnancy test done ≤ 21 days prior to CT simulation, for women of child bearing potential only.

v. Ability to understand and willingness to sign a written informed consent document.

vi. Must have received immunotherapy (PD-1/PD-L1 and/or CTLA-4 inhibitor(s)) within the past 6 months or plan on receiving immunotherapy within the next 1 month.

vii. Must have a Gustave Roussy Immune Score (GRIm-Score) of 0 or 1 (neutrophil-to-lymphocyte ratio > 6 = 1 point, LDH > Upper Limit of Normal = 1 point, and Albumin < 3.5 g/dL = 1 point).

Exclusion Criteria:

i. Diagnosis of germ cell tumor or hematologic malignancy. ii. Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts).

iii. Diagnosis of leptomeningeal disease. iv. Prior SRS to an immediately adjacent lesion(s) of interest or to the current lesion(s) of interest.

v. Prior history of pseudoprogression or radionecrosis from cranial radiotherapy.

vi. A neurosurgical resection cavity deemed too large by the radiation oncologist to be treated with a single fraction of stereotactic radiosurgery.

vii. Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker, eGFR <30, gadolinium allergy).

viii. A Gustave Roussy Immune Score (GRIm-Score) > 1 (neutrophil-to-lymphocyte ratio > 6 = 1 point, LDH > Upper Limit of Normal = 1 point, and Albumin < 3.5 g/dL = 1 point).

Sites / Locations

University Of Chicago

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A

ARM B

Arm Description

Outcomes

Primary Outcome Measures

Multi-Fraction SRS superiority compared to single fraction SRS

To determine if Multi-Fraction SRS will decrease the rate of radionecrosis when compared to single-fraction SRS for patients with small metastases and are on immunotherapy.

Secondary Outcome Measures

Target metastasis progression

Target metastasis progression will be assessed using adapted Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) consensus imaging criteria. In brief, progressive disease is defined as a ≥20% relative increase in the longest diameter (LD) of the target metastasis compared to its smallest LD recorded on study, with a minimum absolute increase of 5 mm

Overall Survival Rate

Time from randomization to death

Acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities

Any acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).

Late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities

Any late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, greater than 90 days from SRS completion (toxicity must be specified).

rate of individual metastases radionecrosis

To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis

rate of individual metastases rates of edema

To compare rates over time of individual metastases rates of edema using a parametric survival analysis.

Rates of Symptomatic Edema

To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1

Time to any distant intracranial failure

Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).

Time to initiation of any combination

Time to initiation of any combination of death, salvage SRS, WBRT, or neurosurgical resection for intracranial failure.

Full Information

NCT ID

NCT04427228

First Posted

June 8, 2020

Last Updated

August 24, 2023

Sponsor

University of Chicago

1. Study Identification

Unique Protocol Identification Number

NCT04427228

Brief Title

Single vs Multi-fraction SRS Patients on Immunotherapy

Acronym

MIGRAINE

Official Title

MIGRAINE: Randomized trIal of Single Versus Multifraction Radiosurgery on Immunotherapy

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Withdrawn

Why Stopped

unable to enroll

Study Start Date

June 29, 2020 (Actual)

Primary Completion Date

December 12, 2022 (Actual)

Study Completion Date

December 12, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

This study is meant to compare different surgical approaches to brain cancer.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Brain Cancer, Brain Metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Care Provider

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm A

Arm Type

Experimental

Arm Title

ARM B

Arm Type

Active Comparator

Intervention Type

Radiation

Intervention Name(s)

Radiosurgery Single Treatment

Other Intervention Name(s)

SRS

Intervention Description

Frameless single-fraction SRS. One large treatment done on each brain tumor. 20 Gy for GTVs (or resection cavity CTVs) < 2 cm, and 18 Gy for GTVs (or resection cavity CTVs) between 2-3 cm in the single-fraction.

Intervention Type

Radiation

Intervention Name(s)

Radiosurgery Three Treatments

Other Intervention Name(s)

SRS

Intervention Description

Multi-fraction SRS. Three small doses done on each brain tumor. 27 Gy in 3 fractions in the multi-fraction group

Primary Outcome Measure Information:

Title

Multi-Fraction SRS superiority compared to single fraction SRS

Description

To determine if Multi-Fraction SRS will decrease the rate of radionecrosis when compared to single-fraction SRS for patients with small metastases and are on immunotherapy.

Time Frame

4 years

Secondary Outcome Measure Information:

Title

Target metastasis progression

Description

Time Frame

4 years

Title

Overall Survival Rate

Description

Time from randomization to death

Time Frame

4 years

Title

Acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities

Description

Any acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).

Time Frame

4 years

Title

Late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities

Description

Any late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, greater than 90 days from SRS completion (toxicity must be specified).

Time Frame

4 years

Title

rate of individual metastases radionecrosis

Description

To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis

Time Frame

4 years

Title

rate of individual metastases rates of edema

Description

To compare rates over time of individual metastases rates of edema using a parametric survival analysis.

Time Frame

4 years

Title

Rates of Symptomatic Edema

Description

To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1

Time Frame

1 year

Title

Time to any distant intracranial failure

Description

Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).

Time Frame

4 years

Title

Time to initiation of any combination

Description

Time to initiation of any combination of death, salvage SRS, WBRT, or neurosurgical resection for intracranial failure.

Time Frame

4 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: i. Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more. ii. Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-10 newly diagnosed intraparenchymal brain metastases. iii. Well-circumscribed, measureable intraparenchymal brain metastasis(s) with maximum tumor diameter ≤3.0 cm. If multiple metastases are present, the other(s) must not exceed 3.0 cm in maximum diameter. At least one metastasis must be ≥ 0.5 cm in maximum diameter to be considered measurable disease. iv. Negative urine or serum pregnancy test done ≤ 21 days prior to CT simulation, for women of child bearing potential only. v. Ability to understand and willingness to sign a written informed consent document. vi. Must have received immunotherapy (PD-1/PD-L1 and/or CTLA-4 inhibitor(s)) within the past 6 months or plan on receiving immunotherapy within the next 1 month. vii. Must have a Gustave Roussy Immune Score (GRIm-Score) of 0 or 1 (neutrophil-to-lymphocyte ratio > 6 = 1 point, LDH > Upper Limit of Normal = 1 point, and Albumin < 3.5 g/dL = 1 point). Exclusion Criteria: i. Diagnosis of germ cell tumor or hematologic malignancy. ii. Metastases in the brain stem, midbrain, pons, medulla, or within 7 mm of the optic apparatus (optic nerves, chiasm and optic tracts). iii. Diagnosis of leptomeningeal disease. iv. Prior SRS to an immediately adjacent lesion(s) of interest or to the current lesion(s) of interest. v. Prior history of pseudoprogression or radionecrosis from cranial radiotherapy. vi. A neurosurgical resection cavity deemed too large by the radiation oncologist to be treated with a single fraction of stereotactic radiosurgery. vii. Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker, eGFR <30, gadolinium allergy). viii. A Gustave Roussy Immune Score (GRIm-Score) > 1 (neutrophil-to-lymphocyte ratio > 6 = 1 point, LDH > Upper Limit of Normal = 1 point, and Albumin < 3.5 g/dL = 1 point).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven Chmura, MD

Organizational Affiliation

University of Chicago

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

12. IPD Sharing Statement

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Single vs Multi-fraction SRS Patients on Immunotherapy

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