Clinical trial NCT04047602: Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
Official title: Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Brain Tumor
Brain Metastases
Brain Cancer
Keywords: Radiation
Immune therapy
Stereotactic Radiosurgery
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2019-08-07
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will evaluate the rate of radiation necrosis following treatment with immune checkpoint inhibitor (ICI) treatment and radiation therapy in subjects with metastatic brain cancer. Subjects will be treated with the standard of care immunotherapy followed by radiation therapy via stereotactic radiosurgery at a reduced dose.

Detailed description: This is a prospective, single arm, pilot study to determine the symptomatic radiation necrosis rate at 6 months utilizing dose-reduced stereotactic radiosurgery with immunotherapy for subjects with a diagnosis of 1-10 brain metastases from MRI and tissue diagnosis of primary malignancy.

Primary end-point is 6 month symptomatic radiation necrosis, defined as a 6-month rate of clinical symptomatology requiring steroid administration (i.e. Decadron) and/or operative intervention concomitant with advanced and routine brain imaging findings consistent with radiation necrosis. Follow-up MRIs will be fused with the planning scan for this assessment.

Eligibility criteria: Inclusion Criteria:

1. Brain MRI-confirmed 1-10 solid tumor brain metastases
2. Biopsy-confirmed primary malignancy
3. ds-GPA estimated median survival of at least 6 months, for histologies not included in the ds-GPA, publications or noted online at brainmetgpa.com, the PI will use either published or validated data or their best clinical judgment to determine the patient's expected survival
4. Stereotactic radiosurgery candidate per treating Radiation Oncologist
5. ≥ 18 years old at the time of informed consent
6. Ability to provide written informed consent and HIPAA (Health Insurance Portability and Accountability Act) authorization.
7. ALC \> 800/ul (Ku et al., 2010)
8. Patients currently on cytotoxic chemotherapy are eligible
9. Patients receiving ICI up to 30 days prior to delivery of SRS are eligible
10. Patients having undergone operative resection for metastatic brain disease within 30 days of immune checkpoint inhibitor (ICI) administration are eligible.

Exclusion Criteria:

1. Major medical illnesses or psychiatric impairments, which in the investigator's opinion will prevent administration or completion of the protocol therapy and/or interfere with follow-up
2. Patients unable to receive MRI Brain
3. Patients with more than 10 brain metastases on MRI Brain imaging
4. Any lesion \> 4 centimeter maximum diameter
5. Total volume of metastatic disease more than 30 cubic centimeters
6. Previous whole brain radiation therapy
7. For Cohort 1: Previous stereotactic radiosurgery where the 50% isodose line overlaps with current treatment field
8. For Cohort 2: Patients whose treatment will have a dose overlap within the target from prior treatments of 20% or greater
9. Already receiving chronic dexamethasone (chronic = \> 2 weeks) prior to SRS
10. Not a radiosurgical candidate per Radiation Oncology discretion
11. Existing autoimmune disease
12. Patients who have an unknown primary cancer
13. Histology not amenable for SRS (i.e. lymphoma). (Small Cell Lung Cancer IS amenable.)

Primary outcomes:
measure: Symptomatic Radiation Necrosis Proportion
timeFrame: 6 months
Secondary outcomes:
measure: Symptomatic Radiation Necrosis Rate
timeFrame: 6 months
measure: Symptomatic Radiation Necrosis Rate
timeFrame: 12 months
measure: Symptomatic Radiation Necrosis by SRS Group
timeFrame: 12 months
measure: Symptomatic Radiation Necrosis by Brain Metastases Group
timeFrame: 12 months
measure: Symptomatic Radiation Necrosis by Immune Checkpoint Inhibitor (ICI) Group
timeFrame: 12 months
measure: Local Control
timeFrame: 6 months
measure: Local Control
timeFrame: 12 months
measure: Local Control by SRS Group
timeFrame: 12 months
measure: Local Control by Brain Metastases Group
timeFrame: 12 months
measure: Local Control by Immune Checkpoint Inhibitor (ICI) Group
timeFrame: 12 months
measure: Radiographic Radiation Necrosis Rate
timeFrame: 6 months
measure: Radiographic Radiation Necrosis Rate
timeFrame: 12 months
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University Methodist Hospital
state: Indiana
city: Portland
country: United States
facility: Oregon Health and Sciences
state: Oregon
Study officials:
affiliation: Indiana University
name: Kevin Shiue, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: McClelland S 3rd, Lautenschlaeger T, Zang Y, Hanna NH, Shiue K, Kamer AP, Agrawal N, Ellsworth SG, Rhome RM, Watson GA. Radiosurgery dose reduction for brain metastases on immunotherapy (RADREMI): A prospective phase I study protocol. Rep Pract Oncol Radiother. 2020 Jul-Aug;25(4):500-506. doi: 10.1016/j.rpor.2020.04.007. Epub 2020 Apr 23.