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

Primary Purpose

Malignant Neoplasm, Brain, Brain Tumor

Status
Withdrawn
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Quality-of-Life Assessment
Questionnaire Administration
Stereotactic Radiosurgery
Therapeutic Conventional Surgery
Sponsored by
Jonsson Comprehensive Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Malignant Neoplasm, Brain

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCLA / Jonsson Comprehensive Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A (SRS/SRT, surgery)

Arm B (surgery, SRS/SRT)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
August 21, 2019
Last Updated
January 14, 2022
Sponsor
Jonsson Comprehensive Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT04069910
Brief Title
Stereotactic Radiation Therapy Before Surgery for the Treatment of Resectable Brain Metastases
Official Title
Neoadjuvant Stereotactic Radiation Therapy for Resectable Brain Metastases
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Withdrawn
Why Stopped
no enrollment
Study Start Date
August 26, 2019 (Actual)
Primary Completion Date
November 30, 2020 (Actual)
Study Completion Date
November 30, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jonsson Comprehensive Cancer Center

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malignant Neoplasm, Brain, Brain Tumor

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A (SRS/SRT, surgery)
Arm Type
Experimental
Arm Description
Patients undergo 1, 5, or 10 fraction of SRS/SRT radiation. Surgery is performed within 72 hours of radiation therapy.
Arm Title
Arm B (surgery, SRS/SRT)
Arm Type
Active Comparator
Arm Description
Within 2-5 weeks after standard of care surgery, patients undergo 1, 5, or 10 fraction of SRS/SRT.
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Radiosurgery
Other Intervention Name(s)
Stereotactic External Beam Irradiation, stereotactic external-beam radiation therapy, stereotactic radiation therapy, Stereotactic Radiotherapy, stereotaxic radiation therapy, stereotaxic radiosurgery
Intervention Description
Undergo SRS/SRT
Intervention Type
Procedure
Intervention Name(s)
Therapeutic Conventional Surgery
Intervention Description
Undergo standard of care surgery
Primary Outcome Measure Information:
Title
Rate of leptomeningeal failure
Description
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.
Time Frame
Up to 2 years
Secondary Outcome Measure Information:
Title
Time to progression
Description
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.
Time Frame
Up to 2 years
Title
Rate of salvage treatment including surgery, SRS, SRT, or WBRT
Description
Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years
Title
Dose (Gy) and volume (cc) of radiation to adjacent normal brain parenchyma
Description
Will be compared using t test for continuous outcomes, log rank test for time-to-event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years
Title
Rate of symptomatic radiation necrosis/steroid dependency
Description
Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years
Title
Rate of distant brain failure
Description
Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years
Title
Overall survival (OS)
Description
Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years
Title
Death due to neurological causes
Description
Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years
Title
Quality of life assessment: FACTBR
Description
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.
Time Frame
Up to 2 years
Title
Genetic expression profiles in pre vs post radiation tumor tissue
Description
Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tania B Kaprealian, MD
Organizational Affiliation
UCLA / Jonsson Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
UCLA / Jonsson Comprehensive Cancer Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States

12. IPD Sharing Statement

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

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