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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 : Not yet recruiting
First Posted : August 28, 2019
Last Update Posted : November 8, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center

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.

Condition or disease Intervention/treatment Phase
Malignant Neoplasm, Brain Brain Tumor Other: Quality-of-Life Assessment Other: Questionnaire Administration Radiation: Stereotactic Radiosurgery Procedure: Therapeutic Conventional Surgery Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 124 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Neoadjuvant Stereotactic Radiation Therapy for Resectable Brain Metastases
Estimated Study Start Date : September 1, 2020
Estimated Primary Completion Date : September 1, 2021
Estimated Study Completion Date : September 1, 2022

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 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

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 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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04069910


Contacts
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Contact: Vincent Basehart 310-267-8954 VBasehart@mednet.ucla.edu

Locations
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United States, California
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, United States, 90095
Contact: Tania B. Kaprealian    310-825-9771      
Principal Investigator: Tania B. Kaprealian         
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Tania B Kaprealian UCLA / Jonsson Comprehensive Cancer Center
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Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT04069910    
Other Study ID Numbers: 17-000082
NCI-2019-05337 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
17-000082 ( Other Identifier: UCLA / Jonsson Comprehensive Cancer Center )
P30CA016042 ( U.S. NIH Grant/Contract )
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: November 8, 2019
Last Verified: August 2019

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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
Additional relevant MeSH terms:
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Brain Neoplasms
Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases