Single vs Multi-fraction SRS Patients on Immunotherapy

Phase 2

Withdrawn

• Conditions: Brain Cancer; Brain Metastases
• Interventions: Radiation: Radiosurgery Single Treatment; Radiation: Radiosurgery Three Treatments

• Registration Number: NCT04427228
• Lead Sponsor: University of Chicago

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-06-08
• Study First Submitted QC: 2020-06-08
• Study First Posted: 2020-06-11
• Study Start: 2020-06-29
• Primary Completion: 2022-12-12
• Study Completion: 2022-12-12
• Status Verified: 2023-08
• Last Update Submitted: 2023-08-24
• Last Update Posted: 2023-08-28

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ARM B	Radiosurgery Single Treatment	-
Arm A	Radiosurgery Three Treatments	-

Primary Outcome Measures

Name	Time	Method
Multi-Fraction SRS superiority compared to single fraction SRS	4 years	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

Name	Time	Method
Overall Survival Rate	4 years	Time from randomization to death
rate of individual metastases rates of edema	4 years	To compare rates over time of individual metastases rates of edema using a parametric survival analysis.
Late CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities	4 years	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	4 years	To compare the rates over time of individual metastases radionecrosis using a parametric survival analysis
Target metastasis progression	4 years	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
Time to any distant intracranial failure	4 years	Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).
Acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities	4 years	Any acute CTCAE v5.0 CNS Grade 2+ and Grade 3+ toxicities, within 90 days of SRS completion (toxicity must be specified).
Time to initiation of any combination	4 years	Time to initiation of any combination of death, salvage SRS, WBRT, or neurosurgical resection for intracranial failure.
Rates of Symptomatic Edema	1 year	To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1

Trial Locations

Locations (1)

University Of Chicago; 🇺🇸 Chicago, Illinois, United States