Neoadjuvant Radiosurgery for Resectable Brain Metastases: Phase I/II Study

This Phase I/II trial studies the ability to stop brain metastases from coming back after treatment with radiosurgery followed by surgical resection. It will also evaluate the side effects of these combined treatments and help determine the best radiosurgery dose. Radiosurgery focuses the x-rays directly to the tumor and cause less damage to the normal tissue in the brain.

Study Overview

• Status: Recruiting
• Conditions: Tumors Metastatic to Brain
• Intervention / Treatment: Procedure: quality-of-life assessment; Procedure: therapeutic conventional surgery; Radiation: radiosurgery

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the safety (risk of acute and long-term toxicities) of neoadjuvant radiosurgery at escalating doses followed by surgical resection of brain metastases. (Phase I)

II. To determine the local control of brain metastases treated with neoadjuvant radiosurgery followed by surgical resection. (Phase II)

SECONDARY OBJECTIVES:

I. To determine the rate of distant brain failure when brain metastases are managed with neoadjuvant radiosurgery followed by surgical resection.

II. To estimate the rate of salvage surgery, whole brain radiation therapy (WBRT), or stereotactic radiosurgery (SRS) for participants treated with neoadjuvant radiosurgery followed by surgical resection.

III. To determine the rate of radiation necrosis/steroid dependency. IV. To determine the radiobiologic impact of neoadjuvant radiosurgery for resected brain metastases.

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

The following outcomes were removed from the protocol in an amendment:

• Changes in neurocognitive function as measured by the Hopkins Verbal Learning Test (HVLT), Controlled Oral Word Association (COWA) & Trailmaking Test B, and Trailmaking Test A
• QOL measured by FACT-BR and EORTC-QLQ30

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Erin Murphy, MD; Phone Number: 1-866-223-8100; Email: TaussigResearch@ccf.org

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic, Case Comprehensive Cancer Center
      • Principal Investigator: Erin Murphy, MD
      • Contact: Erin Murphy, MD; Phone Number: 866-223-8100; Email: TaussigResearch@ccf.org
    • Cleveland, Ohio, United States, 44106
      • Withdrawn
      • University Hospitals Cleveland Medical Center, 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:

• Have a prior histologic diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies
• Magnetic resonance imaging (MRI) evidence of 1-4 brain metastases, with at least one lesion > 20 mm and ≤ 50 mm in maximal diameter and determined to be appropriate for SRS and gross total resection; all other brain metastases are appropriate for SRS
• Patient can have prior SRS to lesions other than the one planned for neoadjuvant SRS and resection
• Patient must have a Karnofsky performance score of ≥ 70

Exclusion Criteria:

• Patient deemed medically unfit to undergo surgical resection of brain metastasis
• Prior whole brain radiotherapy
• Patient with contraindication for imaging with MRI
• Inability to participate in study activities due to physical or mental limitations
• Inability or unwillingness to return for all the required follow-up visits
• At the time of planning, unable to deliver 10 Gray (Gy) or less to optic nerve/chiasm
• Tumor located in the brainstem
• Imaging or cytologic evidence of leptomeningeal disease

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 (radiosurgery, surgery); Patients undergo radiosurgery on day 0. Within 2 weeks, patients undergo surgical resection.	Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment; Procedure: therapeutic conventional surgery; Undergo surgical resection; Radiation: radiosurgery; Undergo radiosurgery; Other Names: radiation surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose (MTD)	MTD of radiosurgery determined by dose-limiting toxicities graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 (Phase I)	Day 0
Proportion of participants without local failure (Phase II)	Local control of brain metastases, as measured by proportion of participants without local failure (Local failure is tumor progression of the metastasis treated on the study) (Phase II) The Kaplan-Meier method will be used.	Up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with distant brain failure	Rate of distant brain failure, defined as progression of brain metastases outside of the brain metastasis treated on study. The Kaplan-Meier method will be used.	Up to 3 years
Rate of radiation necrosis/steroid dependency	Rate of radiation necrosis/steroid dependency	Up to 3 years
Rate of salvage treatment	Number of patients that have any salvage treatment, including surgery, stereotactic radiosurgery (SRS), or whole brain radiation therapy (WBRT)	Up to 3 years

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Investigators: Principal Investigator: Erin Murphy, MD, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 3, 2013
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 28, 2013
• First Posted (Estimated): July 3, 2013

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

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; Investigative Techniques; Therapeutics; Surgical Procedures, Operative; Radiotherapy; Stereotaxic Techniques; Neurosurgical Procedures; Radiosurgery
• Other Study ID Numbers: CASE7312

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes