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

Phase 1

Recruiting

• Conditions: Tumors Metastatic to Brain
• Interventions: Radiation: radiosurgery; Procedure: therapeutic conventional surgery; Procedure: quality-of-life assessment

• Registration Number: NCT01891318
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2013-06-26
• Study First Submitted QC: 2013-06-28
• Study Start: 2013-07-03
• Study First Posted: 2013-07-03
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-11
• Primary Completion: 2025-06-01
• Study Completion: 2025-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (radiosurgery, surgery)	radiosurgery	Patients undergo radiosurgery on day 0. Within 2 weeks, patients undergo surgical resection.
Treatment (radiosurgery, surgery)	therapeutic conventional surgery	Patients undergo radiosurgery on day 0. Within 2 weeks, patients undergo surgical resection.
Treatment (radiosurgery, surgery)	quality-of-life assessment	Patients undergo radiosurgery on day 0. Within 2 weeks, patients undergo surgical resection.

Primary Outcome Measures

Name	Time	Method
Proportion of participants without local failure (Phase II)	Up to 3 years	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.
Maximum tolerated dose (MTD)	Day 0	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)

Secondary Outcome Measures

Name	Time	Method
Proportion of participants with distant brain failure	Up to 3 years	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.
Rate of salvage treatment	Up to 3 years	Number of patients that have any salvage treatment, including surgery, stereotactic radiosurgery (SRS), or whole brain radiation therapy (WBRT)
Rate of radiation necrosis/steroid dependency	Up to 3 years	Rate of radiation necrosis/steroid dependency

Trial Locations

Locations (2)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic, Case Comprehensive Cancer Center; 🇺🇸 Cleveland, Ohio, United States