RECRUITING

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

Conditions

NSCLC Renal Cell Carcinoma Breast Carcinoma Melanoma Brain Metastases, Adult Non-small Cell Lung Cancer SCLC Small-cell Lung Cancer Gamma Knife Linear Accelerator Immune Checkpoint Inhibitor (ICI) therapy Stereotactic Radiosurgery (SRS)Fractionated Stereotactic Radiosurgery (FSRS)Stereotactic Radiosurgery (SSRS)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Hypofractionated Radiotherapy vs Single Fraction Radiosurgery for Brain Metastasis Patients on Immunotherapy (HYPOGRYPHE)

Quick Facts

Study Start:2023-07-11

Study Completion:2028-03-31

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05703269

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. * 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	* 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.

Inclusion Criteria

Exclusion 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.
* 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

* 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.

Contacts and Locations

Study Contact

Karen Craver, MT, MHA

CONTACT

336-716-0891

NCORP@wakehealth.edu

Principal Investigator

Christina K Cramer, MD

PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Study Locations (Sites)

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 South

Saint Louis, Missouri, 63128

United States

Mercy Hospital Springfield

Springfield, Missouri, 65804

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

Bronx, New York, 10461

United States

Montefiore Medical Center-Weiler Hospital

Bronx, New York, 10461

United States

Montefiore Medical Center - Moses Campus

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

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

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

Collaborators and Investigators

Sponsor: Wake Forest University Health Sciences

Christina K Cramer, MD, PRINCIPAL_INVESTIGATOR, Wake Forest University Health Sciences

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-11

Study Completion Date2028-03-31

Study Record Updates

Study Start Date2023-07-11

Study Completion Date2028-03-31

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

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