Can spreading out brain radiation reduce side effects for immunotherapy patients?

NCT ID NCT05703269

Symptom relief Sponsor: Wake Forest University Health Sciences Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This study looks at two ways to give radiation to brain tumors in people who are also receiving immunotherapy for cancers like lung, breast, kidney, or melanoma. The standard approach gives one high dose of radiation, while the experimental approach gives smaller doses over several days. The goal is to see if spreading out the radiation lowers the chance of side effects like brain swelling. About 58 adults with brain metastases will take part.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: radiation therapy (single fraction vs fractionated stereotactic radiosurgery)
What this could lead to: If fractionated radiation works better, it could become a new standard to reduce brain swelling and other side effects for patients on immunotherapy.
What could go wrong: This is a small, early-phase study with only 58 participants, so results may not apply to everyone. The benefit may be small or not seen at all.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Not a phased trial

Phase numbers describe drug development. The registry uses this when they do not apply, as it does for trials of devices, procedures or behaviour changes, and for observational studies.

Participants

58 people

The number who actually took part.

Started

Jul 2023

Expected to finish

Mar 2028

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * 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. * Ability to understand and the willingness to sign written informed consent. * Patients must be able to provide informed consent. * Must be able to speak, read and understand English or Spanish Exclusion Criteria: * 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.

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Conditions

The condition(s) this trial relates to.

brain cancer breast cancer breast carcinoma breast neoplasm melanoma metastatic malignant neoplasm in the brain non-small cell lung carcinoma renal cell carcinoma small cell lung carcinoma

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Brain metastases, adult Breast carcinoma Melanoma Non-small cell lung cancer NSCLC Renal cell carcinoma SCLC Small cell lung cancer

Contacts and locations

Locations

Aspirus Cancer Care - James Beck Cancer Center

Rhinelander, Wisconsin, 54501, United States
Aspirus Cancer Care - Stevens Point

Stevens Point, Wisconsin, 54481, United States
Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin, 54494, United States
Aspirus Langlade Hospital

Antigo, Wisconsin, 54409, United States
Aspirus Regional Cancer Center

Wausau, Wisconsin, 54401, United States
Atrium Health Cabarrus/LCI-Concord

Concord, North Carolina, 28025, United States
Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States
Crossroads Cancer Center

Effingham, Illinois, 62401, United States
Decatur Memorial Hospital

Decatur, Illinois, 62526, United States
Genesys Hurley Cancer Institute

Flint, Michigan, 48503, United States
Gibbs Cancer Center-Pelham

Greer, South Carolina, 29651, United States
HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, 62269, United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, 31405, United States
Lovelace Medical Center-Saint Joseph Square

Albuquerque, New Mexico, 87102, United States
Lovelace Radiation Oncology

Albuquerque, New Mexico, 87109, United States
Mercy Health - Perrysburg Hospital

Perrysburg, Ohio, 43551, United States
Mercy Hospital South

St Louis, Missouri, 63128, United States
Mercy Hospital Springfield

Springfield, Missouri, 65804, United States
OSF Saint Francis Medical Center

Peoria, Illinois, 61637, United States
Prisma Health Cancer Institute - Faris

Greenville, South Carolina, 29605, United States
Saint Francis Cancer Center

Greenville, South Carolina, 29607, United States
Saint Francis Hospital

Greenville, South Carolina, 29601, United States
Saint Joseph's/Candler - Bluffton Campus

Bluffton, South Carolina, 29910, United States
Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States
Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States
Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, 57104, United States
Sanford Roger Maris Cancer Center

Fargo, North Dakota, 58122, United States
Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States
Spartanburg Medical Center

Spartanburg, South Carolina, 29303, United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, 48114, United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, 48197, United States
Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, 48106, United States
Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, 48154, United States
Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

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