Stereotactic Radiosurgery Dose Escalation for Brain Metastases
ConditionBrain Metastases
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of Utah
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
Prior whole 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.
Trial design
Design model
Single group
Treatments tested in this trial
Stereotactic Radiosurgery
RadiationPatients 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.
Treatment groups
86 Participants
are divided into 1 treatment groupGroup A: Stereotactic RadiosurgeryExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Maximum Tolerated Dose of stereotactic radiosurgery
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.
Time frame
Maximum Tolerated Dose of stereotactic radiosurgery will be evaluated throughout the treatment period which is expected to last 12-16 weeks per patient2
Frequency of Adverse Events (AEs)
up to 16 weeks
Time frame
up to 16 weeksSecondary outcomes
1
Frequency of immediate, acute, and chronic central nervous system (CNS) toxicities
To assess the immediate, acute, and chronic central nervous system (CNS) toxicities of single fraction external beam irradiation at increased doses to brain metastases.
Time frame
up to18 months following SRS2
Response of the treated lesion(s)
To evaluate the response of the treated lesion(s) by volume assessment.
Time frame
up to 16 weeks3
Distant brain failures outside of the treated site
To evaluate distant brain failures outside of the treated site.
Time frame
up to 16 weeks4
Overall Survival
To evaluate overall survival of patients for 18 months following SRS.
Time frame
up to18 months following SRSSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Utah
Lead sponsor
Huntsman Cancer Institute
Collaborator
Source ClinicalTrials.gov