Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study

Brain Tumor Clinical Trial

— RADREMI  

Official title:

Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04047602
• Other study ID #: RAON-IIR-IUSCC-0710
• Status: Completed
• Phase: N/A
• Start date: December 12, 2019
• Est. completion date: February 20, 2024

Study information

• Verified date: April 2024
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 20, 2024
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.)

Related Conditions & MeSH terms

• Brain Cancer
• Brain Metastases
• Brain Neoplasms
• Brain Tumor
• Neoplasm Metastasis

Intervention

Radiation:
• Reduced Dose SRS
Subjects will receive SRS treatment at a reduced dose based on the brain tumor size

Locations

Country	Name	City	State
United States	Indiana University Health Hospital	Indianapolis	Indiana
United States	Indiana University Methodist Hospital	Indianapolis	Indiana
United States	Oregon Health and Sciences	Portland	Oregon

Sponsors (1)

Lead Sponsor	Collaborator
Indiana University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Symptomatic radiation necrosis rate	Defined as the 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	6 months post SRS
Secondary	Local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by Response Assessment in Neuro-oncology (RANO) criteria within the planning target volume	6 months, 12 months post SRS
Secondary	Radiographic radiation necrosis rate	Defined as brain imaging findings on magnetic resonance imaging (MRI), magnetic resonance (MR) perfusion, MR Spectroscopy, and/or positron emission tomography (PET) imaging consistent with radiation necrosis.	6 months, 12 months post SRS
Secondary	Symptomatic radiation necrosis rate	Defined as the 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	12 months post SRS
Secondary	Gamma Knife local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who receive SRS via gamma knife techniques	12 months post SRS
Secondary	Linear accelerator local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who receive SRS via linear accelerator techniques	12 months post SRS
Secondary	Multi agent immune checkpoint inhibitor local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who are treated with multi-agent immune checkpoint inhibitor therapy.	12 months post SRS
Secondary	Single agent immune checkpoint inhibitor local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects who are treated with single agent immune checkpoint inhibitor therapy.	12 months post SRS
Secondary	Melanoma brain metastases local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects with metastatic melanoma	12 months post SRS
Secondary	Non-melanoma brain metastases local control rate	Defined as the rate of any new, recurrent, or progressing tumor as defined by RANO criteria within the planning target volume in subjects with non melanoma metastatic disease	12 months post SRS
Secondary	Gamma knife symptomatic radiation necrosis rate	Defined as the 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 in subjects who receive SRS using gamma knife techniques	12 months post SRS
Secondary	Linear accelerator symptomatic radiation necrosis rate	Defined as the 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 in subjects who receive SRS using linear accelerator techniques	12 months post SRS
Secondary	Single agent immune checkpoint inhibitor symptomatic radiation necrosis rate	Defined as the 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 in subjects who are treated with single agent immune checkpoint inhibitor therapy	12 months post SRS
Secondary	Multi agent immune checkpoint inhibitor symptomatic radiation necrosis rate	Defined as the 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 in subjects who are treated with multi agent immune checkpoint inhibitor therapy	12 months post SRS
Secondary	Non melanoma brain metastases symptomatic radiation necrosis rate	Defined as the 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 in subjects with metastatic melanoma	12 months post SRS
Secondary	Melanoma brain metastases symptomatic radiation necrosis rate	Defined as the 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 in subjects with non melanoma metastatic disease	12 months post SRS