Stereotactic Radiosurgery Dose Escalation for Brain Metastases

May 4, 2026 updated by: University of Utah

Phase I Study of Stereotactic Radiosurgery Dose Escalation for Brain Metastases

This is a Phase I dose escalation and expansion trial. The purpose of this study is to determine the maximum tolerated dose of radiation received during stereotactic radiosurgery in patients with brain metastases who have never received radiation to the brain before.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Huntsman Cancer Institute
        • Contact:
        • Principal Investigator:
          • Lindsay Burt, MD

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.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Clinically confirmed brain metastases by CT or MRI criteria. If there is evidence of extra-cranial metastatic disease, it is preferable that the lesions be pathologically confirmed (see section 4.2.5 for excluded histologies) and reviewed by a University of Utah or Huntsman Cancer Hospital pathologist if the initial review was done at an outside facility.
  • Prior brain surgery is allowed, although a lesion situated in the operative bed would not be selected to receive an experimental dose of SRS treatment. SRS should be delivered 4-6 weeks post-surgery if the patient had a craniotomy for resection of a lesion. Enrollment of a patient with the goal of performing SRS outside of the 4-6 post-craniotomy window is at the PI's discretion.
  • Patients must have 1-5 untreated brain metastases total.

  • For patients planning to enroll in Cohort 1a (including expansion) or Cohort 1b: Tumor volume ≤ 4.1888 cm3 by CT or MRI measurement at the time of consultation/screening for the metastatic lesion on trial. Patients who have at least one additional lesion that is larger than the lesions eligible for the expansion cohort, but who are unable to find another open cohort, will have the eligible lesion(s) treated in the expansion cohort, and the remaining lesion(s) treated at the standard dose.

    • For patients enrolling in the expansion Cohort 1a: Up to five brain metastases with tumor volume ≤ 0.5237 cm3 by CT or MRI measurement at the time of consultation/screening will be treated on trial with the MTD. Brain metastases with volume > 0.5237 cm3 will be treated by standard of care SRS dosing.
    • For patients enrolling in Cohort 1b: Tumor volume of > 0.5237 cm3 and ≤ 4.1888 cm3 by CT or MRI measurement at the time of consultation/screening for the metastatic lesion on trial. All other brain metastases will be treated by standard of care SRS dosing.
  • As of Protocol Version 9, Cohorts 2 and 3 are permanently closed to accrual. For patients planning to enroll in Cohort 2 or 3: Equivalent tumor diameter ≤ 40 mm by CT or MRI measurement at the time of consultation/screening for the metastatic lesion on trial. Equivalent tumor diameter </=40 mm by CT or MRI measurement for all lesions treated by standard of care SRS dosing.
  • All metastatic lesions must be separated by a minimum of 3 cm as measured from the peripheral edges of the lesions that are in closest proximity to one another. If multiple lesions are present and are not all ≥ 3 cm away from each other, the patient will be deemed ineligible.
  • Prior systemic therapy is allowed, although appropriate washout is required for patients who have been on BRAF inhibitors (at least 7 days).
  • For subjects currently on active systemic cancer therapy, the treating medical oncologist should be consulted to ensure proper washout (if appropriate) periods prior to SRS.
  • Patients must be at least 18 years of age.
  • Karnofsky Performance Status (KPS) ≥ 60.
  • Able to provide informed consent and have signed an approved consent form that conforms to federal and institutional guidelines.
  • Women of child-bearing potential must have a negative pregnancy test within 10 days of study enrollment and must agree to use an acceptable method of birth control while receiving radiation and for 3 months after radiation. Women of non-childbearing potential may be included if they are either surgically sterile or have been postmenopausal for >1 year.
  • Men who are able to father a child must agree to use an acceptable method of birth control while receiving radiation, and for 3 months after radiation.

Exclusion Criteria:

  • Prior whole/partial brain irradiation.
  • Brain lesions with an equivalent diameter of > 40 mm in size on MRI imaging at the time of consultation/screening for protocol eligibility.
  • Lesions located in anatomic regions that are not amendable to SRS (e.g., optic nerve)
  • Brain lesions located in the brain stem.
  • Radiographic or cytologic evidence of leptomeningeal disease
  • Primary lesion with radiosensitive histology that includes the following: small cell carcinoma, germ cell tumors, lymphoma, leukemia, or multiple myeloma
  • Women of child-bearing potential who are pregnant or breast feeding
  • Patients with multiple lesions, which by size criteria would be enrolled in a cohort which is full at the time of enrollment and the 12-16 weeks DLT period has not been reached.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Stereotactic Radiosurgery
Radiation: Stereotactic Radiosurgery

Patients with 1 to 5 brain metastases will be treated. Patients will be assigned to one of four cohorts based on the size of their brain lesions. For each patient, a single lesion will be treated at experimental dose level, other metastases (if present) will receive standard SRS doses.

Dose Level 1 Dose Level 2 Dose Level 3 Dose Level 4 Cohort 1a and 1a Expansion (starting at Dose Level 3) Diameter: ≤ 10 mm Volume: ≤ 0.5236 cm3 26 Gy 28 Gy 30 Gy n/a Cohort 1b Diameter: 11-20 mm Volume: 0.5237-4.1888 cm3 26 Gy 28 Gy 30 Gy n/a *Cohort 2 Diameter: 21-30 mm Volume: 4.1889-14.1372 cm3 20 Gy 22 Gy 24 Gy n/a

**Cohort 3 Diameter: 31-40 mm Volume: 14.1373-33.5103 cm3 17 Gy 19 Gy 21 Gy 23 Gy

Dose Escalation A non-standard 5+4 design will be used for the dose escalation. For each cohort, an initial group of 5 patients will be accrued at dose level 1 and receive experimental treatment to one of their lesions.

Other Names:
  • SRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose of stereotactic radiosurgery
Time Frame: Maximum Tolerated Dose of stereotactic radiosurgery will be evaluated throughout the treatment period which is expected to last 12-16 weeks per patient

To determine the maximum tolerated dose (MTD) of stereotactic radiosurgery (SRS) treatment for patients in the Escalation Cohort (with 1 to 5 brain metastases, who have not received prior whole brain radiotherapy) and patients in the Expansion Cohort (with up to 5 metastases per patient).

Maximum Tolerated Dose of stereotactic radiosurgery will be evaluated throughout the treatment period which is expected to last 12-16 weeks per patient Patients will be evaluated for any grade 3 or greater toxicities attributed to the lesion treated with the escalated dose.
Maximum Tolerated Dose of stereotactic radiosurgery will be evaluated throughout the treatment period which is expected to last 12-16 weeks per patient
Frequency of Adverse Events (AEs)
Time Frame: up to 16 weeks
up to 16 weeks
up to 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of immediate, acute, and chronic central nervous system (CNS) toxicities
Time Frame: up to18 months following SRS
To assess the immediate, acute, and chronic central nervous system (CNS) toxicities of single fraction external beam irradiation at increased doses to brain metastases.
up to18 months following SRS
Response of the treated lesion(s)
Time Frame: up to 16 weeks
To evaluate the response of the treated lesion(s) by volume assessment.
up to 16 weeks
Distant brain failures outside of the treated site
Time Frame: up to 16 weeks
To evaluate distant brain failures outside of the treated site.
up to 16 weeks
Overall Survival
Time Frame: up to18 months following SRS
To evaluate overall survival of patients for 18 months following SRS.
up to18 months following SRS

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Utah

Collaborators

Huntsman Cancer Institute

Investigators

  • Principal Investigator: Lindsay Burt, MD, Huntsman Cancer Institute/ University of Utah

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 Major Dates

Study Start (Actual)

May 7, 2015

Primary Completion (Estimated)

April 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

March 10, 2015

First Submitted That Met QC Criteria

March 10, 2015

First Posted (Estimated)

March 17, 2015

Study Record Updates

Last Update Posted (Actual)

May 8, 2026

Last Update Submitted That Met QC Criteria

May 4, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HCI71940

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Brain Metastases

Clinical Trials on Stereotactic Radiosurgery

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Ireland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe