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

MIGRAINE: Randomized trIal of Single Versus Multifraction Radiosurgery on Immunotherapy

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

Study Overview

• Status: Withdrawn
• Conditions: Brain Cancer; Brain Metastases
• Intervention / Treatment: Radiation: Radiosurgery Three Treatments; Radiation: Radiosurgery Single Treatment

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Benjamin Onderdonk, MD; Phone Number: 773-702-6870; Email: bonderdonk@radonc.uchicago.edu

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A	Radiation: Radiosurgery Three Treatments; Multi-fraction SRS. Three small doses done on each brain tumor. 27 Gy in 3 fractions in the multi-fraction group; Other Names: SRS
Active Comparator: ARM B	Radiation: Radiosurgery Single Treatment; 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.; Other Names: SRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	4 years
Overall Survival Rate	Time from randomization to death	4 years
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).	4 years
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).	4 years
rate of individual metastases radionecrosis	To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis	4 years
rate of individual metastases rates of edema	To compare rates over time of individual metastases rates of edema using a parametric survival analysis.	4 years
Rates of Symptomatic Edema	To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1	1 year
Time to any distant intracranial failure	Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).	4 years
Time to initiation of any combination	Time to initiation of any combination of death, salvage SRS, WBRT, or neurosurgical resection for intracranial failure.	4 years

Collaborators and Investigators

• Sponsor: University of Chicago
• Investigators: Principal Investigator: Steven Chmura, MD, University of Chicago

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2020
• Primary Completion (Actual): December 12, 2022
• Study Completion (Actual): December 12, 2022

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: June 8, 2020
• First Posted (Actual): June 11, 2020

Study Record Updates

• Last Update Posted (Actual): August 28, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: IRB19-2022

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes