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

• Sponsor: Indiana University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT04047602
• Collaborator: (none)
• Enrollment: 42
• Locations: 3
• Arm: 1
• Anticipated Duration (Months): 52.3
• Patients Per Site: 14
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Brain Tumor; Brain Metastases; Brain Cancer	Radiation: Reduced Dose SRS	N/A

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.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 42 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Radiosurgery Dose Reduction for Brain Metastases on Immunotherapy (RADREMI): A Prospective Pilot Study
• Actual Study Start Date: Aug 21, 2019
• Anticipated Primary Completion Date: Jun 30, 2023
• Anticipated Study Completion Date: Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Reduced Dose Stereotactic Radiosurgery Subjects will receive one stereotactic radiosurgery (SRS) treatment at a reduced dose based on the brain tumor size concurrently with their standard of care immunotherapy. Subjects will undergo follow up with clinical exams and brain MRI scans at 1, 3, 6, 9, and 12 months post SRS treatment	Radiation: Reduced Dose SRS; Subjects will receive SRS treatment at a reduced dose based on the brain tumor size

Outcome Measures

Primary Outcome Measures

1. Symptomatic radiation necrosis rate [6 months post SRS]

   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

Secondary Outcome Measures

1. Local control rate [6 months, 12 months post SRS]

   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

2. Radiographic radiation necrosis rate [6 months, 12 months post SRS]

   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.

3. Symptomatic radiation necrosis rate [12 months post SRS]

   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

4. Gamma Knife local control rate [12 months post SRS]

   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

5. Linear accelerator local control rate [12 months post SRS]

   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

6. Multi agent immune checkpoint inhibitor local control rate [12 months post SRS]

   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.

7. Single agent immune checkpoint inhibitor local control rate [12 months post SRS]

   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.

8. Melanoma brain metastases local control rate [12 months post SRS]

   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

9. Non-melanoma brain metastases local control rate [12 months post SRS]

   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

10. Gamma knife symptomatic radiation necrosis rate [12 months post SRS]

    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

11. Linear accelerator symptomatic radiation necrosis rate [12 months post SRS]

    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. Single agent immune checkpoint inhibitor symptomatic radiation necrosis rate [12 months post SRS]

    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

13. Multi agent immune checkpoint inhibitor symptomatic radiation necrosis rate [12 months post SRS]

    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

14. Non melanoma brain metastases symptomatic radiation necrosis rate [12 months post SRS]

    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

15. Melanoma brain metastases symptomatic radiation necrosis rate [12 months post SRS]

    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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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. This will be assessed by the consenting physician using general questions as outlined in Etchells' publication titled Assessment of Patient Capacity to Consent to Treatment

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

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.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Health Hospital	Indianapolis	Indiana	United States	46202
2	Indiana University Methodist Hospital	Indianapolis	Indiana	United States	46202
3	Oregon Health and Sciences	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Indiana University

Investigators

• Principal Investigator: Kevin Shiue, MD, Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kevin Shiue, MD, Associate Professor of Clinical Radiation Oncology, Indiana University
• ClinicalTrials.gov Identifier: NCT04047602
• Other Study ID Numbers: RAON-IIR-IUSCC-0710
• First Posted: Aug 7, 2019
• Last Update Posted: Mar 31, 2022
• Last Verified: Mar 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Kevin Shiue, MD, Associate Professor of Clinical Radiation Oncology, Indiana University: Radiation; Immune therapy; Stereotactic Radiosurgery
• Additional relevant MeSH terms: Neoplasm Metastasis; Brain Neoplasms

Study Results

No Results Posted as of Mar 31, 2022