Comparing Single vs Multiple Dose Radiation for Cancer Patients With Brain Metastasis and Receiving Immunotherapy
HYPOGRYPHE
Hypofractionated Radiotherapy vs Single Fraction Radiosurgery for Brain Metastasis Patients on Immunotherapy (HYPOGRYPHE)
4 other identifiers
interventional
244
1 country
39
Brief Summary
This study is designed to see if we can lower the chance of side effects from radiation in patients with breast, kidney, small cell lung cancer, non-small cell lung cancer or melanoma that has spread to the brain and who are also being treated with immunotherapy, specifically immune checkpoint inhibitor (ICI) therapy. This study will compare the usual care treatment of single fraction stereotactic radiosurgery (SSRS) given on one day versus fractionated stereotactic radiosurgery (FSRS), which is a lower dose of radiation given over a few days to determine if FSRS is better or worse at reducing side effects than usual care treatment.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for not_applicable
Started Jul 2023
Longer than P75 for not_applicable
39 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 18, 2023
CompletedFirst Posted
Study publicly available on registry
January 30, 2023
CompletedStudy Start
First participant enrolled
July 11, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 31, 2028
February 10, 2026
February 1, 2026
4.7 years
January 18, 2023
February 7, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Occurrence of a Grade 2 or higher Adverse Radiation Effect (ARE)
To compare the proportion of participants experiencing Grade 2 or higher Adverse Radiation Effects (ARE) within 9 months following randomization to single fraction stereotactic radiosurgery (SSRS) vs fractionated stereotactic radiosurgery (FSRS) in patients with brain metastases ≥ 2 cm in diameter or ≥ 4cc in volume treated with concurrent immune checkpoint inhibitor (ICI) therapy.
9 months
Secondary Outcomes (4)
Compare time to composite end point
9 months
Compare time to local failure between SSRS and FSRS groups
9 months
Compare time to neurologic death between groups
9 months
Compare patient-reported brain tumor specific symptom burden
9 months
Study Arms (2)
SSRS = single fraction stereotactic radiosurgery
ACTIVE COMPARATORSSRS is an advanced radiation technique that delivers high dose precision radiation in a single dose to discrete intracranial lesions. SSRS has recently become a standard-of-care treatment for patients with 1-4 brain metastases and is also commonly used for patients with up to 15 metastases, due to improved neurocognitive outcomes compared to whole brain radiotherapy.
FSRS = fractionated stereotactic radiosurgery
EXPERIMENTALFSRS is an advanced radiation technique that uses a lower dose precision radiation delivered over 3 to 5 treatments given daily or every other day to intracranial lesions.
Interventions
SSRS is an advanced radiation technique that delivers high dose precision radiation in a single dose to discrete intracranial lesions.
FSRS is an advanced radiation technique that uses a lower dose precision radiation delivered over 3 to 5 treatments given daily or every other day to intracranial lesions.
Eligibility Criteria
You may qualify if:
- At least one intact brain metastasis or resection cavity ≥ 2 cm in diameter or ≥ 4 cc volume.
- Patients at initial diagnosis of brain metastases and patients with known brain metastasis treated with systemic therapy alone are eligible.
- Patients who have previously undergone SRS for brain metastases are eligible if all MRIs and DICOM-RT files from prior SRS courses are available for upload to TRIAD and there are no lesions requiring re-irradiation. Prior SRS data upload is NOT required prior to enrollment and randomization. Both SSRS and FSRS are acceptable.
- Lesion volume will be approximated by measuring the lesion's three perpendicular diameters on contrast-enhanced, T1-weighted MRI and the product of those diameters will be divided by 2 to estimate the lesion volume (e.g., xyz/2). Alternatively, direct volumetric measurements via slice-by-slice contouring on a treatment planning software package can be used to calculate the total tumor volume.
- Any extent of non-CNS disease is allowed. There is no requirement for non-CNS disease to be controlled prior to study entry.
- For patients considered to be borderline or potentially eligible by size or volume criteria, sites have the option to send in DICOM films for central review screening.
- Age ≥ 18 years at the time of enrollment.
- Total number of brain metastases (including resection cavities) ≤ 15 on diagnostic MRI; all lesions must be amenable to SSRS and FSRS as determined by the treating radiation oncologist. Treatment must take place at a facility credentialed by the Imaging and Radiation Oncology Core (IROC) for SRS and that offers both SSRS and FSRS as treatment options.
- Total gross tumor volume must be ≤ 30 cc. Lesion volume will be approximated by measuring each lesion's three perpendicular diameters on contrast-enhanced T1 MRI and the product of those diameters will be divided by 2 (V = xyz/2). Direct volumetric measurements by contouring all lesions on all visible slices on treatment planning software is also acceptable. If there is a cavity, only gross residual disease within or adjacent to the cavity is counted toward the 30 cc total volume.
- Ability to tolerate MRI brain with gadolinium-based contrast.
- Pathologically confirmed melanoma, renal cell carcinoma, non-small cell lung cancer, small cell lung cancer, or breast cancer.
- Has received, is currently receiving, or is planned to receive immune checkpoint inhibitor therapy (defined as agent targeted to PD-1/PD-L1 axis) within 30 days of the planned first day of SSRS/FSRS. Dual ICI therapy with PD-1/PD-L1 and CTLA-4 targeted agents are allowed, but patients treated with a single agent CTLA-4 targeted agent only are ineligible.
- o It is not mandatory to wait for the results of next generation sequencing (NGS) or other molecular tumor testing to determine if the patient is planned to receive ICI if the enrolling physician feels that identification of a mutation that would preclude ICI therapy (such as an EGFR mutation in a patient with NSCLC) is unlikely to be identified.
- Karnofsky Performance Status (KPS) ≥ 50. Refer to Appendix A.
- Negative serum or urine pregnancy test within 14 days of randomization for women of child-bearing potential.
- +3 more criteria
You may not qualify if:
- Prior fractionated, whole, or partial brain radiation therapy. Prior fractionated SRS is acceptable.
- Prior courses of SRS for benign tumors such as meningiomas, pituitary adenomas, schwannomas may be acceptable if the treatment is \> 2cm away from the site of a metastatic lesion that would be treated on this study. The study PI or a designated co-PI must review this type of case to confirm eligibility prior to enrollment.
- Prior diagnosis ARE, including pseudoprogression or radiation necrosis/radionecrosis, or previously treated lesions being actively evaluated for possible ARE or local failure such as concerning imaging findings currently being tracked with short interval MRI.
- Leptomeningeal carcinomatosis established by lumbar puncture cytology, or MRI imaging. In the absence of a clinical indication, a lumbar puncture is not required to confirm eligibility.
- A brain metastasis that is 5 mm or less from the optic chiasm or optic nerves
- Inability to tolerate brain MRI or receive gadolinium-based contrast
- Planned or prior therapy with bevacizumab (or bevacizumab biosimilar) within 30 days of the planned first day of SRS as part of a systemic therapy regimen at study enrollment.
- Serious intercurrent illness or medical condition judged by the local investigator to compromise the patient's safety, preclude safe administration of the planned protocol treatment, or would not permit the patient to be managed according to the protocol guidelines.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (39)
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, 31405, United States
Decatur Memorial Hospital
Decatur, Illinois, 62526, United States
Crossroads Cancer Center
Effingham, Illinois, 62401, United States
HSHS Saint Elizabeth's Hospital
O'Fallon, Illinois, 62269, United States
OSF Saint Francis Medical Center
Peoria, Illinois, 61637, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor, Michigan, 48106, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan, 48114, United States
Genesys Hurley Cancer Institute
Flint, Michigan, 48503, United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan, 48154, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan, 48197, United States
Mercy Hospital Springfield
Springfield, Missouri, 65804, United States
Mercy Hospital South
St Louis, Missouri, 63128, United States
Overlook Medical Center
Summit, New Jersey, 07901, United States
Lovelace Medical Center-Saint Joseph Square
Albuquerque, New Mexico, 87102, United States
Lovelace Radiation Oncology
Albuquerque, New Mexico, 87109, United States
Montefiore Medical Center-Einstein Campus
The Bronx, New York, 10461, United States
Montefiore Medical Center-Weiler Hospital
The Bronx, New York, 10461, United States
Montefiore Medical Center - Moses Campus
The Bronx, New York, 10467, United States
Carolinas Medical Center/Levine Cancer Institute
Charlotte, North Carolina, 28203, United States
Atrium Health Cabarrus/LCI-Concord
Concord, North Carolina, 28025, United States
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157, United States
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota, 58122, United States
Mercy Health - Perrysburg Hospital
Perrysburg, Ohio, 43551, United States
Saint Elizabeth Youngstown Hospital
Youngstown, Ohio, 44501, United States
Saint Joseph's/Candler - Bluffton Campus
Bluffton, South Carolina, 29910, United States
Saint Francis Hospital
Greenville, South Carolina, 29601, United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605, United States
Saint Francis Cancer Center
Greenville, South Carolina, 29607, United States
Gibbs Cancer Center-Pelham
Greer, South Carolina, 29651, United States
Spartanburg Medical Center
Spartanburg, South Carolina, 29303, United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota, 57104, United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
Aspirus Langlade Hospital
Antigo, Wisconsin, 54409, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Aspirus Cancer Care - James Beck Cancer Center
Rhinelander, Wisconsin, 54501, United States
Aspirus Cancer Care - Stevens Point
Stevens Point, Wisconsin, 54481, United States
Aspirus Regional Cancer Center
Wausau, Wisconsin, 54401, United States
Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids, Wisconsin, 54494, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Glenn Lesser, MD
Wake Forest University Health Sciences
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- SUPPORTIVE CARE
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 18, 2023
First Posted
January 30, 2023
Study Start
July 11, 2023
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
March 31, 2028
Last Updated
February 10, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Time Frame
- 6 months after publication for a 2 year duration
- Access Criteria
- upon request to NCORP@wakehealth.edu
Wake Forest NCORP Research Base is committed to following the NIH Statement on Sharing Research Data (http://grants.nih.gov/grants/guide/ notice-files/NOT-OD-03-032.html). As of July 2018, the WF NCORP RB signed an agreement with NCI to contribute de-identified data and data dictionaries from clinical trials conducted through our RB to the NCI NCTN/NCORP data archive within 6 months of primary and non-primary publications of phase II/III and phase III trials to https://nctn-data-archive.nci.nih.gov/. This will become the primary means for sharing raw data, and we will adhere to the guidelines spelled out in the NCTN/NCORP Data Archive Usage Guide. De-identified data from studies not covered by the agreement (e.g., phase II and observational studies) will be made available upon request. All data files will be de-identified. De-identification procedures will meet the HIPAA criteria as detailed in the Code of Federal Regulations, Part 45, Section 164.514.