Comparing Single vs Multiple Dose Radiation for Cancer Patients With Brain Metastasis and Receiving Immunotherapy

NCT ID: NCT05703269

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

244 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-11

Study Completion Date

2028-03-31

Brief Summary

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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.

Detailed Description

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This study is an open-label, randomized, Phase III trial designed to ascertain whether fractionated stereotactic radiosurgery (FSRS) results in lower incidence of Grade 2 or higher adverse radiation effect (ARE) by 9 months compared to single fraction stereotactic radiosurgery (SSRS) in patients with large brain metastases who have received or will receive immune checkpoint inhibitor (ICI) targeted to the PD-1/PD-L1 axis within 30 days of stereotactic radiosurgery (SRS). Participants will be randomized 1:1 to either SSRS or FSRS, using a minimization randomization strategy considering 5 prognostic factors of interest: radiosurgery platform (gamma knife vs. LINAC), timing of immunotherapy relative to radiation (ICI within 30 days prior to Day 1 of SRS or not), surgical status (any resection cavity vs intact metastases only), predominant tumor type (Melanoma vs. all others), and prior courses of SRS for brain metastases (yes vs. no).

Conditions

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NSCLC Renal Cell Carcinoma Breast Carcinoma Melanoma Brain Metastases, Adult Non-small Cell Lung Cancer SCLC Small-cell Lung Cancer

Keywords

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Gamma Knife Linear Accelerator Immune Checkpoint Inhibitor (ICI) therapy Stereotactic Radiosurgery (SRS) Fractionated Stereotactic Radiosurgery (FSRS) Stereotactic Radiosurgery (SSRS)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Participants will be randomized 1:1 to either SSRS or FSRS, using minimization randomization strategy considering 5 prognostic factors of interest: radiosurgery platform (GK vs. LINAC), timing of immunotherapy relative to radiation (ICI within 30 days of Day 1 prior to SRS or not), surgical status (any resection cavity vs. intact metastases only), predominant tumor type (Melanoma vs. all others), and prior courses of SRS for brain metastases (yes vs. no). All baseline patient-reported outcomes and neurocognitive assessments will be collected prior to randomization to minimize bias.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

Study Groups

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SSRS = single fraction stereotactic radiosurgery

SSRS 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.

Group Type ACTIVE_COMPARATOR

single fraction stereotactic radiosurgery (SSRS)

Intervention Type RADIATION

SSRS is an advanced radiation technique that delivers high dose precision radiation in a single dose to discrete intracranial lesions.

FSRS = fractionated stereotactic radiosurgery

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.

Group Type EXPERIMENTAL

fractionated stereotactic radiosurgery (FSRS)

Intervention Type RADIATION

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.

Interventions

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fractionated stereotactic radiosurgery (FSRS)

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.

Intervention Type RADIATION

single fraction stereotactic radiosurgery (SSRS)

SSRS is an advanced radiation technique that delivers high dose precision radiation in a single dose to discrete intracranial lesions.

Intervention Type RADIATION

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Glenn Lesser, MD

Role: STUDY_CHAIR

Wake Forest University Health Sciences

Locations

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Lewis Cancer and Research Pavilion at Saint Joseph's/Candler

Savannah, Georgia, United States

Site Status RECRUITING

Decatur Memorial Hospital

Decatur, Illinois, United States

Site Status RECRUITING

Crossroads Cancer Center

Effingham, Illinois, United States

Site Status RECRUITING

HSHS Saint Elizabeth's Hospital

O'Fallon, Illinois, United States

Site Status RECRUITING

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Site Status RECRUITING

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

Ann Arbor, Michigan, United States

Site Status RECRUITING

Trinity Health IHA Medical Group Hematology Oncology - Brighton

Brighton, Michigan, United States

Site Status RECRUITING

Genesys Hurley Cancer Institute

Flint, Michigan, United States

Site Status RECRUITING

Trinity Health Saint Mary Mercy Livonia Hospital

Livonia, Michigan, United States

Site Status RECRUITING

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

Ypsilanti, Michigan, United States

Site Status RECRUITING

Mercy Hospital Springfield

Springfield, Missouri, United States

Site Status RECRUITING

Mercy Hospital South

St Louis, Missouri, United States

Site Status RECRUITING

Overlook Medical Center

Summit, New Jersey, United States

Site Status RECRUITING

Lovelace Medical Center-Saint Joseph Square

Albuquerque, New Mexico, United States

Site Status RECRUITING

Lovelace Radiation Oncology

Albuquerque, New Mexico, United States

Site Status RECRUITING

Montefiore Medical Center-Einstein Campus

The Bronx, New York, United States

Site Status RECRUITING

Montefiore Medical Center-Weiler Hospital

The Bronx, New York, United States

Site Status RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

Site Status RECRUITING

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Site Status RECRUITING

Atrium Health Cabarrus/LCI-Concord

Concord, North Carolina, United States

Site Status RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Site Status RECRUITING

Sanford Roger Maris Cancer Center

Fargo, North Dakota, United States

Site Status RECRUITING

Mercy Health - Perrysburg Hospital

Perrysburg, Ohio, United States

Site Status RECRUITING

Saint Elizabeth Youngstown Hospital

Youngstown, Ohio, United States

Site Status WITHDRAWN

Saint Joseph's/Candler - Bluffton Campus

Bluffton, South Carolina, United States

Site Status RECRUITING

Saint Francis Hospital

Greenville, South Carolina, United States

Site Status RECRUITING

Prisma Health Cancer Institute - Faris

Greenville, South Carolina, United States

Site Status RECRUITING

Saint Francis Cancer Center

Greenville, South Carolina, United States

Site Status RECRUITING

Gibbs Cancer Center-Pelham

Greer, South Carolina, United States

Site Status RECRUITING

Spartanburg Medical Center

Spartanburg, South Carolina, United States

Site Status RECRUITING

Sanford Cancer Center Oncology Clinic

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Aspirus Langlade Hospital

Antigo, Wisconsin, United States

Site Status RECRUITING

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

Site Status RECRUITING

Aspirus Cancer Care - James Beck Cancer Center

Rhinelander, Wisconsin, United States

Site Status RECRUITING

Aspirus Cancer Care - Stevens Point

Stevens Point, Wisconsin, United States

Site Status RECRUITING

Aspirus Regional Cancer Center

Wausau, Wisconsin, United States

Site Status RECRUITING

Aspirus Cancer Care - Wisconsin Rapids

Wisconsin Rapids, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Karen Craver, MT, MHA

Role: CONTACT

Phone: 336-716-0891

Email: [email protected]

Facility Contacts

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Other Identifiers

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5UG1CA189824-08

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2022-10836

Identifier Type: REGISTRY

Identifier Source: secondary_id

WF-2201

Identifier Type: OTHER

Identifier Source: secondary_id

IRB00092505

Identifier Type: -

Identifier Source: org_study_id