Preop fSRS for Resectable Brain Metastases

Pre-operative Hypofractionated Stereotactic Radiosurgery for Resectable Brain Metastases

The purpose of the study is to determine whether treatment with pre-operative hypofractionated stereotactic radiosurgery followed by surgery will improve time to local failure (TTLF) compared to the current standard of care.

Study Overview

• Status: Active, not recruiting
• Conditions: Brain Metastases; Brain Lesion
• Intervention / Treatment: Radiation: Hypofractionated Stereotactic Radiosurgery

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed solid tumor malignancy other than lymphoma, or germ cell tumor. Brain biopsy is not required unless diagnosis is judged to be in doubt by the treating physician.
• Life expectancy must be deemed to be 3 months or more by a neurosurgeon, radiation oncologist, or medical oncologist with expertise in the treatment of metastatic cancer to the brain.
• Participants must have MRI evidence of >/=1 brain metastasis no less than 10 mm and no greater than 60 mm in maximum diameter, deemed surgically resectable by neurosurgeon, not previously treated with Stereotactic Radiosurgery (SRS) or appropriate for fSRS.
• Each non-index lesion must be </= 4.0 cm in maximal extent on contrasted MRI scan, and not otherwise require resection. The number of non-index lesions allowed will be at the treating physician's discretion, providing the use of whole brain radiotherapy is not used for treatment of these lesions.
• Participants must be either asymptomatic from their brain metastases or have symptoms which are well controlled with steroid medication.
• Systemic therapy such as immunotherapy, targeted therapy, or chemotherapy are permitted at treating physician's discretion.
• Karnofsky Performance Status (KPS) >/=60.
• This study permits the re-enrollment of participant who has discontinued the study due to pre-treatment failure (i.e., the participant has not been treated). If re-enrolled, participant must be re-consented.
• Women of Childbearing Potential (WOCBP) must have a negative serum or urine pregnancy test within 7 days prior to the start of radiation therapy.
• Azoospermic males and WOCBP whoa re continuously not heterosexually active are exempt from contraceptive requirements. However, they must still undergo pregnancy testing as described.
• Investigators shall counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators shall advise on the use of highly effective methods of contraception (detailed in protocol), which have a failure rate of <1% when used consistently and correctly.

Exclusion Criteria:

• Participants who have germ cell tumors, primary brain tumor, or lymphoma
• Participants with symptoms related to brain metastases not able to be controlled with steroids.
• Women who are pregnant or breastfeeding
• Women of childbearing potential who are not using an effective method of contraception
• Participants deemed medically unfit to undergo surgical resection of brain metastasis by the treating neurosurgeon because of medical comorbidities, such as those who are neurologically or hemodynamically unstable despite appropriate medical interventions.
• Participants who have had whole brain radiation within the previous three months.
• Any prior cranial radiotherapy targeting the index lesion
• Index lesion located in the brainstem
• Any participants with the following imaging findings:

Widespread definitive leptomeningeal metastasis Infratentorial mass effect with fourth ventricle effacement or hydrocephalus Supratentorial mass effect with greater than 10 mm of midline shift or hydrocephalus.

A brain metastasis that is located within 2 mm of the optic chiasm

• Active or prior: documented inherited hypersensitivity syndromes, certain collagen vascular diseases, and certain autoimmune diseases. For example, any radiation hypersensitivity syndrome, including, but not limited to, Gorlin syndrome, multiple sclerosis, ataxia-telangiectasia, scleroderma, and systemic lupus erythematosus.
• Inability to complete MRI with contrast of the brain, or a known allergy to gadolinium
• Participants receiving cytotoxic chemotherapies 7 days prior to or concurrently with fSRS. Note: All other systemic therapies (i.e., molecularly targeted therapies) will be reviewed on a case-by-case basis by study PI to determine if appropriate for study treatment and documented within the research record or EMR.
• If participant's treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
• Inability or unwillingness to return for all the required follow-up visits
• Prisoners or individuals who are involuntarily incarcerated
• Individuals who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Hypofractionated Stereotactic Radiosurgery prior to resection; Participants will be given hypofractionated stereotactic radiosurgery (fSRS) in 9 Gray Units (Gy) per fraction x 3 consecutive daily fractions (27 Gy total) to the index metastasis that will be resected on Days 1-3 (3 consecutive days). If there are additional non index brain metastasis, they will be treated with standard stereotactic radiosurgery at the time of fSRS. Participants will then undergo stereotactic craniotomy for surgical resection of the index metastasis within 5 days following completion of fSRS.

Radiation: Hypofractionated Stereotactic Radiosurgery; Participants will be given hypofractionated stereotactic radiosurgery (fSRS) in 9 Gray Units (Gy) per fraction x 3 consecutive daily fractions (27 Gy total) to the index metastasis that will be resected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from surgery until Intracranial Progression	Time from surgery until first occurrence of Intracranial Progression or death. If none of these events occur, patients will be censored on date of last contact.	up to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Time from surgery to death, censoring at the last contact date if no deaths.	up to 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local Control Rate	Local control rate is defined as the freedom from local progression	at 6 months
Local Control Rate	Local control rate is defined as the freedom from local progression	at 12 months
Rate of Leptomeningeal Disease (LMD)	Rate of LMD is defined as the percentage of participants that progressed to leptomeningeal disease	at 12 months
Rate of distant brain recurrence (DBR)	Rate of distant brain recurrence defined as the percentage of participants that experienced distant brain recurrence	at 12 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Investigators: Principal Investigator: Michael Yu, MD, Moffitt Cancer Center

Publications and helpful links

Helpful Links

• Moffitt Cancer Center Clinical Trials website

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2022
• Primary Completion (Actual): May 29, 2025
• Study Completion (Estimated): August 21, 2026

Study Registration Dates

• First Submitted: February 24, 2022
• First Submitted That Met QC Criteria: February 24, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: MCC-21193

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No