Brain Metastases in Greater Size - Hypofractionated Options Trial (BIGSHOT)

NCT07227610 | Recruiting Phase 2 DMC FDA Device

• 1 other identifier: 104122
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, phase II trial comparing staged stereotactic radiosurgery (SSRS) versus fractionated stereotactic radiotherapy (FSRT) in patients with large brain metastases (≥2 cm and ≤5 cm). The study aims to evaluate efficacy, safety, and tumor response between these two standard-of-care radiation approaches.

Conditions

Brain Metastases; Cancer (With CNS Involvement)

Keywords

Cancer; Brain

Outcome Measures

Primary Outcomes (1)

• Time to Composite unfavorable outcome (CUO) by (1) lack of local control (disease progression for any lesion treated on study); (2) the need for further intervention to the treated tumor; (3) radiation necrosis.

  For lesions \> 5 mm: Disease progression is defined as at least a 50% increase in the product of the two longest diameters of the target lesion, compared to the smallest product measured for that lesion. For lesions ≤ 5mm on the baseline scan, disease progression is defined as at least a 100% increase in the product of the two longest diameters of the target lesion, compared to the smallest product measured for the same lesion. * Radiation necrosis is defined by: pathologic diagnosis after resection or biopsy; OR initiation of steroids, and follow up MRI scan shows decrease in edema and stability of contrast of enhancing lesion that was concerning for radiation necrosis. * Radiation necrosis is NOT counted as disease progression. * Additional interventions include surgical resection, LITT (laser interstitial thermal therapy), or re-irradiation to the target lesion.

  Up to 36 months.

Secondary Outcomes (1)

• Compare the safety profile by radiation toxicity

  Up to 36 months

Study Arms (2)

Staged Stereotactic Radiosurgery (SSRS)

EXPERIMENTAL

Patient will be scheduled for treatment with SSRS within one week of randomization. The large brain metastasis (or metastases) will be treated to a dose of 24-30 Gy in two fractions. Interval between the two fractions will be 30 days (+/- 10 days). MRI brain for planning purposes will be obtained either on the day of each treatment, or within 7 days prior to each treatment. Individual dosing for each fraction will be determined by the treating radiation oncologist, but total dose must equal 24-30 Gy. Any additional smaller metastases will be treated in a single fraction concurrently. Fixation for treatment will be either in a surgical headframe or mask.

Radiation: Staged Stereotactic Radiosurgery (SSRS)

Fractionated Stereotactic Radiotherapy (FSRT)

EXPERIMENTAL

Patient will be scheduled for treatment with FSRT within one week of randomization. FSRT will be performed with mask fixation. Fractionation will be 27 Gy in 3 daily fractions. The 3 daily fractions must be completed over a period of 3-5 days. MRI for planning purposes must be completed within 7 days prior to delivery of first fraction. Any additional smaller metastases will be treated in a single fraction concurrently.

Radiation: Fractionated Stereotactic Radiotherapy (FSRT)

Interventions

Staged Stereotactic Radiosurgery (SSRS) RADIATION

The large brain metastasis (or metastases) will be treated to a dose of 24-30 Gy in two fractions. Interval between the two fractions will be 30 days (+/- 10 days). Individual dosing for each fraction will be determined by the treating radiation oncologist, but total dose must equal 24-30 Gy.

Staged Stereotactic Radiosurgery (SSRS)

Fractionated Stereotactic Radiotherapy (FSRT) RADIATION

Fractionation will be 27 Gy in 3 daily fractions. The 3 daily fractions must be completed over a period of 3-5 days.

Fractionated Stereotactic Radiotherapy (FSRT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient or a legally authorized representative must be able and willing to provide study-specific informed consent prior to study entry.
• Patient must be willing to comply with all study procedures and available for the duration of the study
• Male or female, aged ≥ 18 years
• Karnofsky Performance Status (KPS) ≥ 60 within 7 days prior to registration
• Radiographic confirmation of brain metastasis measuring ≥2 cm and ≤ 5 cm in maximum diameter
• Multiple metastases are allowed. Additional metastases will be treated with single fraction SRS as per standard of care. Up to 10 additional smaller metastases are allowed on protocol. All additional smaller metastases must be less than 2 cm.
• If a patient has more than one large metastasis (measuring between 2 and 5 cm as above), up to two can be treated on study protocol
• All tumors must be ≥ 5mm from the optic chiasm and optic nerves.
• Known active or history of invasive non-CNS primary cancer based on documented pathologic diagnosis within the past 3 years
• Patient is able to medically tolerate SRS
• Patient is neurologically stable (immediate surgery not necessary or not recommended)
• A negative urine or serum pregnancy test (in persons of childbearing potential) within 7 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal.
• Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment on this study to prevent pregnancy.

You may not qualify if:

• Prior cranial radiotherapy, including whole brain radiotherapy (WBRT), or SRS in the area of the large metastasis to be treated on study.
• Inability to undergo MRI with contrast
• Planned administration of systemic therapy (chemotherapy or immunotherapy) within 3 days prior to, the day of, or 3 days after completion of SRS.

Sponsors & Collaborators

• Medical University of South Carolina: lead

Study Sites (1)

Medical University of South Carolina Hollings Cancer Center

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Neoplasms

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Charlotte Rivers, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Central Study Contacts

HCC Clinical Trials Office

CONTACT

843-792-9321; hcc-clinical-trials@musc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 12, 2025
• Study Start: February 3, 2026
• Primary Completion (Estimated): February 3, 2029
• Study Completion (Estimated): February 3, 2030
• Last Updated: February 5, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Time Frame: After completion of the primary endpoint.
• Access Criteria: Requests will be reviewed and approved by the study sponsor. Data will be shared in accordance with institutional and NIH policies.

Locations

US (1)