Stereotactic Radiation Therapy Before Surgery for the Treatment of Resectable Brain Metastases

Neoadjuvant Stereotactic Radiation Therapy for Resectable Brain Metastases

This trial studies how well stereotactic radiation therapy before surgery works in treating patients with cancer that has spread to the brain (brain metastases) and can be removed by surgery (resectable). Stereotactic radiation therapy is a specialized radiation therapy that delivers a single, high dose of radiation directly to the tumor, and may cause less damage to normal tissue. Giving stereotactic radiation therapy before surgery may make the return of brain metastases less likely and help patients live longer compared to surgery followed by radiation therapy.

Study Overview

• Status: Withdrawn
• Conditions: Brain Tumor; Malignant Neoplasm, Brain
• Intervention / Treatment: Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Therapeutic Conventional Surgery; Radiation: Stereotactic Radiosurgery

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the rate of leptomeningeal failure after neoadjuvant radiation therapy (NaRT) versus (vs) postoperative stereotactic radiosurgery (SRS)/stereotactic radiation therapy (SRT).

SECONDARY OBJECTIVES:

I. Local control of brain metastases. II. Rate of salvage treatment including surgery, SRS, SRT, or whole brain radiation therapy (WBRT).

III. Dose and volume of radiation to adjacent normal brain parenchyma. IV. Rate of symptomatic radiation necrosis/steroid dependency. V. Rate of distant brain failure. VI. To compare overall survival (OS) between the 2 groups. VII. To determine the number of patients who die due to neurologic causes. VIII. To assess quality of life as assessed using Functional Assessment of Cancer Therapy?Brain (FACT?BR).

IX. To evaluate and compare the molecular makeup of tumor tissue in pre vs post radiation settings and determine differences in molecular and germline markers.

X. To evaluate biomarkers and germline markers predicting response.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients undergo 1, 5, or 10 fraction of SRS/SRT radiation. Surgery is performed within 72 hours of radiation therapy.

ARM B: Within 2-5 weeks after standard of care surgery, patients undergo 1, 5, or 10 fraction of SRS/SRT.

After completion of study treatment, patients are followed up every 3 months.

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA / Jonsson Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prior histologic diagnosis of cancer other than small cell lung cancer, lymphoma, and germ cell histologies
• 1?4 cerebral metastases per magnetic resonance imaging (MRI) with at least 1 being dominant and eligible for resection
• No prior radiation treatment for the index brain metastases
• Systemic disease staged within previous 8 weeks and not rapidly progressing, with concern of life expectancy > 3 months
• The patients will have been evaluated by the multidisciplinary team, and surgery must be deemed necessary as a result of indications including but not limited to mass effect or symptomatic lesion. Surgery must be deemed non?emergent or non?urgent clinically by the neurosurgeon
• Karnofsky performance status (KPS) >= 70
• No active infections requiring systemic antibiotics
• If a woman is of childbearing potential, a negative serum pregnancy test must be documented. Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) for duration of study participation and for up to 4 weeks following the study treatment
• Ability to understand and willingness to sign a written informed consent

Exclusion Criteria:

• Patient deemed medically unfit to undergo surgical resection of brain metastasis
• Prior whole brain radiotherapy
• Patient with contraindication for imaging with MRI
• Surgery is considered emergent or urgent by the neurosurgeon due to symptoms or concerning mass effect noted on imaging
• Patients who are participating in a concurrent treatment protocol
• At the time of planning, unable to meet dose tolerance of the optic nerve/chiasm
• Tumor located in the brainstem
• Imaging or cytologic evidence of leptomeningeal disease
• Concurrent uncontrolled illness including, but not limited to, any of the following: Symptomatic congestive heart failure, unstable angina pectoris, psychiatric illness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Arm A (SRS/SRT, surgery); Patients undergo 1, 5, or 10 fraction of SRS/SRT radiation. Surgery is performed within 72 hours of radiation therapy.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Therapeutic Conventional Surgery; Undergo standard of care surgery; Radiation: Stereotactic Radiosurgery; Undergo SRS/SRT; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; stereotactic radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery
ACTIVE_COMPARATOR: Arm B (surgery, SRS/SRT); Within 2-5 weeks after standard of care surgery, patients undergo 1, 5, or 10 fraction of SRS/SRT.	Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment; Other: Questionnaire Administration; Ancillary studies; Procedure: Therapeutic Conventional Surgery; Undergo standard of care surgery; Radiation: Stereotactic Radiosurgery; Undergo SRS/SRT; Other Names: Stereotactic External Beam Irradiation; stereotactic external-beam radiation therapy; stereotactic radiation therapy; Stereotactic Radiotherapy; stereotaxic radiation therapy; stereotaxic radiosurgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of leptomeningeal failure	A two-sided Z test with pooled variance will be used at significance level =0.1 to test if there is a difference in leptomeningeal failure rate between the two treatment groups.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to progression	Local control of brain metastases is defined as tumor has not progressed or recurred with no radiographic or symptomatic progression. Using the Response Assessment in Neuro-Oncology (RANO) criteria for brain metastases, progressive disease will be defined as > 20% increase in the sum of the longest diameters of the target lesions; unequivocal progression of enhancing non?target lesions; new lesions; or substantial clinical decline. Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Rate of salvage treatment including surgery, SRS, SRT, or WBRT	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Dose (Gy) and volume (cc) of radiation to adjacent normal brain parenchyma	Will be compared using t test for continuous outcomes, log rank test for time-to-event outcomes and Z test for binary outcomes.	Up to 2 years
Rate of symptomatic radiation necrosis/steroid dependency	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Rate of distant brain failure	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Overall survival (OS)	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Death due to neurological causes	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years
Quality of life assessment: FACTBR	Assessed using Functional Assessment of Cancer Therapy-Brain (FACTBR). Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes. The scale is 0 - 4, 0 = "not at all", 4 = "very much". Overall higher ratings mean higher quality of life.	Up to 2 years
Genetic expression profiles in pre vs post radiation tumor tissue	Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.	Up to 2 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Investigators: Principal Investigator: Tania B Kaprealian, MD, UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 26, 2019
• Primary Completion (ACTUAL): November 30, 2020
• Study Completion (ACTUAL): November 30, 2020

Study Registration Dates

• First Submitted: August 21, 2019
• First Submitted That Met QC Criteria: August 23, 2019
• First Posted (ACTUAL): August 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2022
• Last Update Submitted That Met QC Criteria: January 14, 2022
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms; Brain Neoplasms
• Other Study ID Numbers: 17-000082; NCI-2019-05337 (REGISTRY: CTRP (Clinical Trial Reporting Program))

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.: Yes