Pre-operative Stereotactic Radiosurgery Followed by Resection for Patients With Brain Metastases

A Phase II Study Analyzing Pre-operative Stereotactic Radiosurgery Followed by Resection for Patients With 1 - 4 Brain Metastases

This is a prospective, single arm, phase II trial to determine the local control at 6 months utilizing pre-operative stereotactic radiosurgery followed by surgery within 1 - 4 days in subjects with a diagnosis of 1-4 brain metastases and with an indication for surgical resection of at least one brain metastasis at the discretion of a neurosurgeon.

Study Overview

• Status: Completed
• Conditions: Brain Metastases
• Intervention / Treatment: Procedure: Radiosurgery

Detailed Description

Primary Objective To evaluate 6 month in-brain local control utilizing pre-operative stereotactic radiosurgery followed by surgical resection for brain metastases.

Secondary Objectives

• Overall survival
• Distant in-brain progression
• Rate of leptomeningeal spread
• Rate of radiation necrosis

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Methodist Hospital
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Melvin and Bren Simon Comprehensive Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Radiographically confirmed solid tumor brain metastases
2. Criteria for surgical resection of at least one metastasis per neurosurgeon discretion
3. A diagnostic MRI Brain or CT Head demonstrating the presence of 1-4 solid tumor brain metastases and lesion to be resected no more than 5 cm in any direction, performed within 30 days prior to stereotactic radiosurgery. If multiple lesions are present, then the total brain metastases volume can be no more than 30 cm3 excluding the lesion to be resected.
4. For known primary included in brainmetgpa.com, an estimated median survival no less than 6 months per brainmetgpa.com
5. For unknown primary or known primary not included within brainmetgpa.com, an estimated median survival no less than 6 months per PI discretion Note: If patient's estimated median survival is calculated using a histology that is different than the histology demonstrated in final pathology, the patient may remain eligible for all study endpoints per PI discretion
6. Surgical candidate per neurosurgeon discretion
7. Surgical resection able to be performed within 1 - 4 days after radiosurgery
8. Stereotactic radiosurgery candidate per radiation oncologist
9. ≥ 18 years old at the time of informed consent
10. Ability to provide written informed consent and HIPAA authorization. This will be assessed by the consenting physician using general questions to determine the patient's ability to understand the medical problem, proposed treatment, alternatives to proposed treatment, and understand the consequences of the medical choices.
11. Platelet count > 100 k/cumm, Hgb > 7.5 gm/dL, INR < 1.3, ANC > 1.5 k/cumm
12. Patients currently on cytotoxic chemotherapy or immunotherapy are eligible, not including anti-VEGF therapy
13. If a patient who meets all stated eligibility criteria is enrolled on study and then discovered to be ineligible, the tissue obtained will still be deemed eligible to remain in study for evaluation.

Exclusion Criteria

1. Patients who received anti-VEGF therapy within 6 weeks prior to enrollment, as there is increased risk of fatal brain hemorrhage with surgical resection
2. Major medical illnesses or psychiatric impairments, which in the investigator's opinion will prevent administration or completion of the protocol therapy and/or interfere with follow-up
3. Patients with more than 4 brain metastases on MRI Brain or CT Head
4. Lesion to be resected is more than 5 cm
5. Total volume of metastatic disease more than 30 cm3 excluding lesion to be resected
6. Patients with leptomeningeal metastases documented by MRI or CSF evaluation
7. Previous whole brain radiation therapy
8. Previous radiation therapy to lesion to be resected
9. Planned adjuvant focal therapy including additional radiation therapy to the brain
10. Not a surgical candidate per neurosurgeon's discretion
11. Not a radiosurgical candidate per radiation oncologist's discretion
12. Surgery unable to be performed between 1 - 4 days after radiosurgery
13. Women who are pregnant or nursing are not eligible as treatment involves unforeseeable risks to the fetus or child

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: Arm 1; This is a single arm study so this arm will include all eligible subjects. All subjects will have radiosurgery 1-4 days prior to surgical resection.

Procedure: Radiosurgery; Stereotactic radiosurgery will be delivered on all patients utilizing gamma knife or linear accelerator based techniques as per RTOG-9005 dosing criteria (Section 11 Table 1) based on tumor diameter with the exception that the largest lesion diameter to be treated with 15 Gy will be 5 cm. All apparent, previously untreated brain metastases will be treated with radiosurgery at this time. Radiosurgery will be performed 1-4 days prior to surgical resection. Vital signs and MRI Brain planning scan will be performed on the day of radiosurgery prior to the procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of local control of any new, recurrent, or progressing tumors within the planning target volume	Measured by post-treatment MRI	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of overall survival	Time from start of treatment to death of any cause	6 months, 1 year, and 2 years
Rate of in-brain progression free survival	Time from start of treatment to any in-brain	6 months, 1 year, and 2 years
Proportion of patients with distant in-brain failure (any new parenchymal lesion outside of the planning target volume)	Measured by post-treatment MRI	2 years
Proportion of patients with radiation necrosis (radiographic or biopsy-positive diagnosis of radiation necrosis)	Measured by post-treatment MRI	2 years
Proportion of patients with leptomeningeal spread (radiographic or CSF diagnosis of leptomeningeal disease)	Measured by post-treatment MRI	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory: Correlation of RNA biomarkers	Correlation of RNA biomarkers with local control	2 yrs

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Namita Agrawal, MD, Indiana University School of Medicine

Publications and helpful links

General Publications

• Huff WX, Agrawal N, Shapiro S, Miller J, Kulwin C, Shah M, Savage JJ, Payner T, Vortmeyer A, Watson G, Dey M. Efficacy of pre-operative stereotactic radiosurgery followed by surgical resection and correlative radiobiological analysis for patients with 1-4 brain metastases: study protocol for a phase II trial. Radiat Oncol. 2018 Dec 20;13(1):252. doi: 10.1186/s13014-018-1178-8.

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2018
• Primary Completion (Actual): August 26, 2022
• Study Completion (Actual): May 21, 2024

Study Registration Dates

• First Submitted: January 8, 2018
• First Submitted That Met QC Criteria: January 8, 2018
• First Posted (Actual): January 12, 2018

Study Record Updates

• Last Update Posted (Actual): July 16, 2024
• Last Update Submitted That Met QC Criteria: July 14, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Neoplastic Processes; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasm Metastasis; Brain Neoplasms
• Other Study ID Numbers: IUSCC-0627; 1707314702 (Other Identifier: Indiana University IRB)

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: No
• product manufactured in and exported from the U.S.: No