Fractionated Stereotactic Radiosurgery for Large Brain Metastases

PHASE I STUDY OF FRACTIONATED STEREOTACTIC RADIOSURGERY FOR LARGE BRAIN METASTASES

This is a research trial that seeks to break up the total radiation dose into multiple smaller radiation treatments, termed fractionated stereotactic radiosurgery (FSRS) which may make the treatment feasible. Fractionated sterotatcic radiation, the risks of FSRS, and possible costs will be described later in this document. This clinical trial is for people who have had no prior whole brain radiation.

Study Overview

• Status: Completed
• Conditions: Large Brain Mets
• Intervention / Treatment: Radiation: Fractionated Stereotactic Radiosurgery

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Shadyside Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female patients ≥ 18 years of age
• A life expectancy of at least 12 weeks with a Karnofsky performance status of at least 70 (Appendix II)
• The target lesion(s) can be accurately measured in at least one dimension according to RECIST
• No prior radiotherapy to the brain
• Previous or concurrent systemic or targeted chemotherapy is allowed
• Patients must have an extra-cranial primary tumor diagnosis
• Patients will have no more than 3 distinct lesions within the brain. At least 1 lesion must be a minimum of 3cm in greatest dimension, no larger than 5cm which will be treatable by fractionated stereotactic radiosurgery
• The additional lesions will each be treated with single fraction stereotactic radiosurgery
• Patient may be on steroids or anti-epileptics
• Must be aware of the neoplastic nature of his/her disease and willingly provide written, informed consent after being informed of the procedure to be followed, the experimental nature of the therapy, alternatives, potential benefits, side-effects, risks and discomforts
• Patients do not need a histologically proven diagnosis of brain mets

Exclusion Criteria:

• Symptomatic patients in need of surgery to the "target" lesion
• Four or more newly-diagnosed lesions
• Prior surgical resection of targeted tumor
• Prior WBRT
• Primary brain tumor
• Pregnant or breast-feeding patients
• Primary tumor histology of lymphoma, leukemia, multiple myeloma or germ cell tumor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Fractionated Stereotactic Radiosurgery; 24 to 36 Gy in 3 fractions (8-12 Gy/fx).	Radiation: Fractionated Stereotactic Radiosurgery; SRS SBRT CyberKnife Trilogy True Beam Radiosurgery; Other Names: SBRT; CyberKnife; Trilogy; True Beam; Radiosurgery; SRS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients Experiencing DLT	The number of patients experiencing DLT, defined as the maximum amount of Gy fractionated stereotactic radiosurgery (FSRS) delivered without significant toxicity.	Up to 3 years
Maximum Tolerated Dose (MTD)	The MTD was determined following a Time-to-Event Continual Reassessment Model which models toxicity as a function of dose. Treatment was given in 3 fractions (8-12 Gy/fx).	Up to 24 months post completion of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Best Response	Percentage of patients with Complete Response (CR), Partial Response (PR), or Stable Disease (SD) in the target lesion, or Progressive Disease (PD) per RECIST v1.1. (CR): the disappearance of a target lesion. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. (PR): at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study. (PD): at least a 20% increase in the sum of diameters of target lesions, taking as a reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (the appearance of one or more new lesions is also considered progression).	Up to 24 months after completion of treatment
Local Control of Disease	Percentage of patients with local control, defined as stable disease (SD), partial response (PR), or complete response (CR) in the target lesion, per RECIST v1.1. Complete Response (CR): the disappearance of a target lesion. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm., Partial Response (PR): at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum diameters while on study.	Up to 24 months after completion of treatment
Regional Intracranial Failure	Percentage of patients who develop new lesions outside the target volume. Patients without follow-up scans are excluded as it is not known if they developed lesions outside the target volume.	Up to 24 months after completion of treatment
Functional Assessment of Cancer Therapy - Brain (FACT-Br)	Functional Assessment of Cancer Therapy - Brain (FACT-Br) is a 50 item, self-administered questionnaire used to assess Quality of Life, including, Physical Well-Being, Social/Family Well-Being, Emotional Well-Being, and Functional Well-Being. Subscale scores range from 0-4. FACT-G = (PWB - 7 items, score range 0-28) + (SWB - 7 items, score range 0-28) + (EWB - 6 items, score 0-24) + (FWB - 7 items, 0-28). The assessment takes 10-15 minutes to completed and is scored using a 5-point Likert-type scale. Scores range from 0-108, with higher scores indicating better Quality of Life.	Prior to treatment; 30 days post treatment; 8 -12 weeks, 22-28 weeks, 30-42 weeks, 45-60 weeks, 64-74 weeks, 80-84 weeks, 90-96 weeks,100-112 weeks, 120-124 weeks, 130-140 weeks, 145-155 weeks, and 160-170 weeks post treatment

Collaborators and Investigators

• Sponsor: Steven Burton
• Investigators: Principal Investigator: Steve Burton, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2013
• Primary Completion (Actual): November 20, 2017
• Study Completion (Actual): March 9, 2023

Study Registration Dates

• First Submitted: January 30, 2014
• First Submitted That Met QC Criteria: January 31, 2014
• First Posted (Estimated): February 4, 2014

Study Record Updates

• Last Update Posted (Actual): May 28, 2025
• Last Update Submitted That Met QC Criteria: May 8, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms; Brain Neoplasms
• Other Study ID Numbers: HCC 11-091

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