Phase I Study of Stereotactic Radiosurgery Dose Escalation for Brain Metastases

University of Utah1 site in 1 country50 target enrollmentMay 7, 2015

ConditionsBrain Metastases

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Brain Metastases
Sponsor: University of Utah
Enrollment: 50
Locations: 1
Primary Endpoint: Maximum Tolerated Dose of stereotactic radiosurgery
Status: Recruiting
Last Updated: 12 months ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

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.

Registry

clinicaltrials.gov

Start Date

May 7, 2015

End Date

April 2026

Last Updated

12 months ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

University of Utah

Responsible Party

Sponsor

Eligibility Criteria

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.

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 weeks DLT period has not been reached.

Outcomes

Primary Outcomes

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 weeks per patient

Patients will be evaluated for any grade 3 or greater toxicities attributed to the lesion treated with the escalated dose