Staged stereotactic radiosurgery versus fractionated stereotactic radiotherapy for larger brain metastases

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

This trial tests whether staged stereotactic radiosurgery or fractionated stereotactic radiotherapy better controls brain metastases 2–5 cm in adults while reducing side effects.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Medical University of South Carolina (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, radiation
• Locations: 1 site (Charleston, South Carolina)
• Trial ID: NCT07227610 on ClinicalTrials.gov

What this trial studies

This is a randomized phase II trial that compares two standard focused radiation approaches—staged stereotactic radiosurgery (SSRS) and fractionated stereotactic radiotherapy (FSRT)—for patients with brain metastases between 2 and 5 cm. Participants are assigned to one of the two radiation schedules and are followed for measures of tumor response, local control, and treatment-related toxicity. The protocol allows up to two large lesions on study and up to ten additional smaller metastases treated per standard single-fraction SRS. The trial is conducted at the Medical University of South Carolina Hollings Cancer Center with regular imaging and clinical follow-up visits to track outcomes.

Who should consider this trial

Good fit: Adults (≥18 years) with one or up to two brain metastases measuring between 2 and 5 cm, Karnofsky Performance Status ≥60, tumors at least 5 mm from the optic chiasm/optic nerves, and ability to attend treatment and follow-up at the study site are ideal candidates.

Not a fit: Patients with lesions larger than 5 cm, tumors closer than 5 mm to the optic chiasm or optic nerves, poor performance status (KPS <60), or who cannot travel to the Charleston clinic are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the trial could identify the radiation approach that gives better tumor control with fewer side effects, helping patients preserve brain function and avoid whole-brain radiation.

How similar studies have performed: Stereotactic radiosurgery is well proven for lesions under 2 cm and both staged and fractionated strategies are used for larger tumors, but randomized direct comparisons between these two approaches are limited.

Eligibility criteria

Inclusion Criteria:

1. The patient or a legally authorized representative must be able and willing to provide study-specific informed consent prior to study entry.
2. Patient must be willing to comply with all study procedures and available for the duration of the study
3. Male or female, aged ≥ 18 years
4. Karnofsky Performance Status (KPS) ≥ 60 within 7 days prior to registration
5. Radiographic confirmation of brain metastasis measuring ≥2 cm and ≤ 5 cm in maximum diameter

   1. 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.
   2. 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
   3. All tumors must be ≥ 5mm from the optic chiasm and optic nerves.
6. Known active or history of invasive non-CNS primary cancer based on documented pathologic diagnosis within the past 3 years
7. Patient is able to medically tolerate SRS
8. Patient is neurologically stable (immediate surgery not necessary or not recommended)
9. 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.
10. Participants who are sexually active must agree to use medically acceptable forms of contraception during treatment on this study to prevent pregnancy.

Exclusion Criteria:

1. Prior cranial radiotherapy, including whole brain radiotherapy (WBRT), or SRS in the area of the large metastasis to be treated on study.
2. Evidence of leptomeningeal disease (LMD) Note: For the purposes of exclusion, LMD is a clinical diagnosis, defined as positive CSF cytology and/or unequivocal radiologic or clinical evidence of leptomeningeal involvement. Patients with leptomeningeal symptoms in the setting of leptomeningeal enhancement by imaging (MRI) would be considered to have LMD even in the absence of positive CSF cytology. In contrast, an asymptomatic or minimally symptomatic patient with mild or nonspecific leptomeningeal enhancement (MRI) would not be considered to have LMD. In such cases, CSF sampling is not required to formally exclude LMD, but can be performed at the investigator's discretion based on level of clinical suspicion.
3. Inability to undergo MRI with contrast
4. Planned administration of systemic therapy (chemotherapy or immunotherapy) within 3 days prior to, the day of, or 3 days after completion of SRS.

Where this trial is running

Charleston, South Carolina

• Medical University of South Carolina Hollings Cancer Center — Charleston, South Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Charlotte Rivers, MD — Medical University of South Carolina
• Study coordinator: HCC Clinical Trials Office

Conditions Brain Metastases; Cancer; Brain