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

Purpose

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.

Conditions

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Randomized
Intervention Model
Sequential Assignment
Intervention Model Description
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 Purpose
Supportive Care
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
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.
  • 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.
Experimental
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.
  • Radiation: 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.

Recruiting Locations

Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah 4221552, Georgia 4197000 31405
Contact:
912-819-5704
underberga@sjchs.org

Decatur Memorial Hospital
Decatur 4236895, Illinois 4896861 62526
Contact:
217-876-4762
morganthaler.jodi@mhsil.com

Crossroads Cancer Center
Effingham 4237727, Illinois 4896861 62401
Contact:
217-876-4762
morganthaler.jodi@mhsil.com

HSHS Saint Elizabeth's Hospital
O'Fallon 4245926, Illinois 4896861 62269
Contact:
217-876-4762
morganthaler.jodi@mhsil.com

OSF Saint Francis Medical Center
Peoria 4905687, Illinois 4896861 61637
Contact:
309-243-3605
andersonj@illinoiscancercare.com

Trinity Health Saint Joseph Mercy Hospital Ann Arbor
Ann Arbor 4984247, Michigan 5001836 48106
Contact:
734-712-7251
MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton 4986994, Michigan 5001836 48114
Contact:
734-712-7251
MCRCwebsitecontactform@stjoeshealth.org

Genesys Hurley Cancer Institute
Flint 4992982, Michigan 5001836 48503
Contact:
810-762-8038
wstrong@ghci.org

Trinity Health Saint Mary Mercy Livonia Hospital
Livonia 4999837, Michigan 5001836 48154
Contact:
734-712-7251
MCRCwebsitecontactform@stjoeshealth.org

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti 5015688, Michigan 5001836 48197
Contact:
734-712-7251
MCRCwebsitecontactform@stjoeshealth.org

Mercy Hospital Springfield
Springfield 4409896, Missouri 4398678 65804
Contact:
417-269-4520

Mercy Hospital South
St Louis 4407066, Missouri 4398678 63128
Contact:
314-525-6042
Danielle.Werle@mercy.net

Lovelace Medical Center-Saint Joseph Square
Albuquerque 5454711, New Mexico 5481136 87102
Contact:
505-272-0530
AYost@nmcca.org

Lovelace Radiation Oncology
Albuquerque 5454711, New Mexico 5481136 87109
Contact:
505-272-0530
AYost@nmcca.org

Carolinas Medical Center/Levine Cancer Institute
Charlotte 4460243, North Carolina 4482348 28203
Contact:
800-804-9376

Atrium Health Cabarrus/LCI-Concord
Concord 4461574, North Carolina 4482348 28025
Contact:
800-804-9376

Wake Forest University Health Sciences
Winston-Salem 4499612, North Carolina 4482348 27157
Contact:
336-713-6771

Sanford Broadway Medical Center
Fargo 5059163, North Dakota 5690763 58122
Contact:
701-323-5760
OncologyClinicalTrialsFargo@sanfordhealth.org

Sanford Roger Maris Cancer Center
Fargo 5059163, North Dakota 5690763 58122
Contact:
701-234-6161
OncologyClinicalTrialsFargo@sanfordhealth.org

Mercy Health - Perrysburg Hospital
Perrysburg 5166516, Ohio 5165418 43551
Contact:
614-488-2745
Jeffh@columbusccop.org

Saint Joseph's/Candler - Bluffton Campus
Bluffton 4571722, South Carolina 4597040 29910
Contact:
912-819-5704
underberga@sjchs.org

Saint Francis Hospital
Greenville 4580543, South Carolina 4597040 29601
Contact:
864-603-6213
melissa_beckman@bshsi.org

Prisma Health Cancer Institute - Faris
Greenville 4580543, South Carolina 4597040 29605
Contact:
864-241-6251

Saint Francis Cancer Center
Greenville 4580543, South Carolina 4597040 29607
Contact:
864-603-6213
melissa_beckman@bshsi.org

Gibbs Cancer Center-Pelham
Greer 4580599, South Carolina 4597040 29651
Contact:
864-560-6104
kmertz-rivera@gibbscc.org

Spartanburg Medical Center
Spartanburg 4597200, South Carolina 4597040 29303
Contact:
864-560-6104
kmertz-rivera@gibbscc.org

Sanford Cancer Center Oncology Clinic
Sioux Falls 5231851, South Dakota 5769223 57104
Contact:
605-312-3320
OncologyClinicTrialsSF@sanfordhealth.org

Sanford USD Medical Center - Sioux Falls
Sioux Falls 5231851, South Dakota 5769223 57117-5134
Contact:
605-312-3320
OncologyClinicalTrialsSF@SanfordHealth.org

Aspirus Langlade Hospital
Antigo 5244010, Wisconsin 5279468 54409
Contact:
715-623-9869
Juli.Alford@aspirus.org

Saint Vincent Hospital Cancer Center Green Bay
Green Bay 5254962, Wisconsin 5279468 54301
Contact:
920-433-8889
WI_research_admin@hshs.org

Aspirus Cancer Care - James Beck Cancer Center
Rhinelander 5268720, Wisconsin 5279468 54501
Contact:
715-847-2353
Beth.Knetter@aspirus.org

Aspirus Cancer Care - Stevens Point
Stevens Point 5274644, Wisconsin 5279468 54481
Contact:
715-847-2353
Beth.Knetter@aspirus.org

Aspirus Regional Cancer Center
Wausau 5278120, Wisconsin 5279468 54401
Contact:
877-405-6866

Aspirus Cancer Care - Wisconsin Rapids
Wisconsin Rapids 5279436, Wisconsin 5279468 54494
Contact:
715-422-7718

More Details

Status
Recruiting
Sponsor
Wake Forest University Health Sciences

Study Contact

Karen Craver, MT, MHA
336-716-0891
NCORP@wfusm.edu

Detailed Description

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).