Clinical trial NCT01891318: Neoadjuvant Radiosurgery for Resectable Brain Metastases: Phase I/II Study
Official title: Neoadjuvant Radiosurgery for Resectable Brain Metastases: Phase I/II Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Tumors Metastatic to Brain
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2013-07-03
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Maximum tolerated dose (MTD)
timeFrame: Day 0
measure: Proportion of participants without local failure (Phase II)
timeFrame: Up to 3 years
Secondary outcomes:
measure: Proportion of participants with distant brain failure
timeFrame: Up to 3 years
measure: Rate of radiation necrosis/steroid dependency
timeFrame: Up to 3 years
measure: Rate of salvage treatment
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: Case Comprehensive Cancer Center
name: Erin Murphy, MD
role: PRINCIPAL_INVESTIGATOR
References: