Single vs Multi-fraction SRS Patients on Immunotherapy

Brain Metastases Clinical Trial

— MIGRAINE  

Official title:

MIGRAINE: Randomized trIal of Single Versus Multifraction Radiosurgery on Immunotherapy

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04427228
• Other study ID #: IRB19-2022
• Status: Withdrawn
• Phase: Phase 2
• Start date: June 29, 2020
• Est. completion date: December 12, 2022

Study information

• Verified date: August 2023
• Source: University of Chicago
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 12, 2022
• Est. primary completion date: December 12, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Brain Cancer
• Brain Metastases
• Brain Neoplasms

Intervention

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

Locations

Country	Name	City	State
United States	University Of Chicago	Chicago	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
University of Chicago

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Overall Survival Rate	Time from randomization to death	4 years
Secondary	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
Secondary	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
Secondary	rate of individual metastases radionecrosis	To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis	4 years
Secondary	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
Secondary	Rates of Symptomatic Edema	To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1	1 year
Secondary	Time to any distant intracranial failure	Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).	4 years
Secondary	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