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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04069910
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : September 18, 2020
Sponsor:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

Tracking Information
First Submitted Date  ICMJE August 21, 2019
First Posted Date  ICMJE August 28, 2019
Last Update Posted Date September 18, 2020
Actual Study Start Date  ICMJE August 26, 2019
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 23, 2019)
Rate of leptomeningeal failure [ Time Frame: Up to 2 years ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 23, 2019)
  • Time to progression [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    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) [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    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 [ Time Frame: Up to 2 years ]
    Will be compared using t test for continuous outcomes, log rank test for time?to?event outcomes and Z test for binary outcomes.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Stereotactic Radiation Therapy Before Surgery for the Treatment of Resectable Brain Metastases
Official Title  ICMJE Neoadjuvant Stereotactic Radiation Therapy for Resectable Brain Metastases
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Malignant Neoplasm, Brain
  • Brain Tumor
Intervention  ICMJE
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • 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
  • Procedure: Therapeutic Conventional Surgery
    Undergo standard of care surgery
Study Arms  ICMJE
  • 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.
    Interventions:
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Stereotactic Radiosurgery
    • Procedure: Therapeutic Conventional Surgery
  • 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.
    Interventions:
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Radiation: Stereotactic Radiosurgery
    • Procedure: Therapeutic Conventional Surgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 23, 2019)
124
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2022
Estimated Primary Completion Date September 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vincent Basehart 310-267-8954 VBasehart@mednet.ucla.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04069910
Other Study ID Numbers  ICMJE 17-000082
NCI-2019-05337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-000082 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jonsson Comprehensive Cancer Center
Study Sponsor  ICMJE Jonsson Comprehensive Cancer Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Tania B Kaprealian, MD UCLA / Jonsson Comprehensive Cancer Center
PRS Account Jonsson Comprehensive Cancer Center
Verification Date September 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP