Stereotactic Radiosurgery in Treating Patients With Large Brain Metastases

Dose Escalation for Larger Brain Metastases: Phase I/II Study

This phase I/II trial studies the side effects and the best dose of stereotactic radiosurgery and to see how well it works in treating patients with large brain metastases. Radiosurgery can send x-rays directly to the tumor and cause less damage to normal tissue.

Study Overview

• Status: Active, not recruiting
• Conditions: Unspecified Adult Solid Tumor; Tumors Metastatic to Brain
• Intervention / Treatment: Procedure: quality-of-life assessment; Radiation: stereotactic radiosurgery; Procedure: cognitive assessment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the incidence of acute and long-term toxicities with increasing dose of stereotactic radiosurgery (SRS). (Phase I) II. To determine if local control may be improved with increasing doses of SRS. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the risk of acute and long-term toxicity with increasing dose of SRS. (Phase II) II. To determine if there is increased neurocognitive toxicity with increased dose of SRS.

III. To determine the rate of radiation necrosis/steroid dependency. IV. To determine if quality of life is affected more by tumor recurrence versus radiation necrosis. This includes assessment of progression free survival, overall survival, local failure, and number of patients who receive bevacizumab, laser interstitial thermal therapy, or surgery for presumed radiation necrosis.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

Patients undergo SRS guided by computer tomography (CT) and magnetic resonance imaging (MRI).

After completion of treatment, patients are followed up at 1-2, 3, 6, 9, and 12 months, every 3 months for 2 years, and then every 4 months thereafter.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Any patient undergoing SRS for brain metastases
• Lesions to be treated under this protocol must be > 2 cm, but =< 4.0 cm in diameter

• Patients may have had prior therapy including:

  • Whole brain radiation therapy (WBRT) > 3 months ago
  • SRS to other brain metastases
• Patients with newly diagnosed brain metastases are eligible as long as they are not planned for WBRT upfront
• Any primary is eligible with exception of small cell lung cancer, lymphoma, and germ cell histologies
• Patient must be able to provide written informed consent

Exclusion Criteria:

• Patients receiving SRS to resection bed
• Planned concurrent WBRT
• Leptomeningeal metastases
• Small cell lung cancer, lymphoma, and germ cell histologies
• Inability to participate in study activities due to physical or mental limitations
• Inability or unwillingness to return for all the required follow-up visits
• Conformality index 2.0 or less cannot be achieved, or homogeneity index is > 2.0
• Unable to deliver 10 Gray (Gy) or less to optic nerve/chiasm
• Brainstem location is excluded from this study

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
Experimental: Treatment (SRS); Patients undergo SRS guided by CT and MRI.	Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Radiation: stereotactic radiosurgery; Undergo SRS; Procedure: cognitive assessment; Ancillary studies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum-tolerated dose based on the incidence of dose-limiting toxicity (DLT) defined as any grade III or IV toxicity as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)	Up to 4 months
Response associated with increased dose of SRS as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase II)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events as assessed by CTCAE version 4.0 (Phase II)	Toxicity will be summarized as frequencies and percentages with a corresponding exact 95% confidence interval.	Up to 2 years
Quality of life (QOL) as assessed by the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and the European Organization for Research and Treatment (EORTC)- Quality of Life Questionnaire Core 30 (QLQ30)		Up to 12 months

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Samuel Chao, MD, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2013
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: April 26, 2013
• First Submitted That Met QC Criteria: April 29, 2013
• First Posted (Estimated): April 30, 2013

Study Record Updates

• Last Update Posted (Actual): July 20, 2025
• Last Update Submitted That Met QC Criteria: July 18, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: unspecified adult solid tumor, protocol specific
• 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: CASE8312

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