MIGRAINE: Single vs Multi-fraction SRS Patients on Immunotherapy
Study Details
Study Description
Brief Summary
This study is meant to compare different surgical approaches to brain cancer.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| 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:
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| 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:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- Overall Survival Rate [4 years]
Time from randomization to death
- 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).
- 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
- 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.
- Rates of Symptomatic Edema [1 year]
To compare rates of symptomatic edema at 3 months, 6 months, and 1 year.1
- Time to any distant intracranial failure [4 years]
Time to any distant intracranial failure (ie, appearance of brain metastasis at untreated site).
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Adult patients (≥ 18 years old) with an ECOG Performance Status 0-2 and a life expectancy of 3 months or more.
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Histologically confirmed systemic malignancy with gadolinium contrast-enhanced MRI scan demonstrating 1-10 newly diagnosed intraparenchymal brain metastases.
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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.
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Negative urine or serum pregnancy test done ≤ 21 days prior to CT simulation, for women of child bearing potential only.
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Ability to understand and willingness to sign a written informed consent document.
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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.
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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:
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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).
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Diagnosis of leptomeningeal disease. iv. Prior SRS to an immediately adjacent lesion(s) of interest or to the current lesion(s) of interest.
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Prior history of pseudoprogression or radionecrosis from cranial radiotherapy.
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A neurosurgical resection cavity deemed too large by the radiation oncologist to be treated with a single fraction of stereotactic radiosurgery.
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Contraindications to gadolinium contrast-enhanced MRI (eg, non-compatible pacemaker, eGFR <30, gadolinium allergy).
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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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Of Chicago | Chicago | Illinois | United States | 60637 |
Sponsors and Collaborators
- University of Chicago
Investigators
- Principal Investigator: Steven Chmura, MD, University of Chicago
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IRB19-2022