Neurocognitive Decline in Patients With Brain Metastases
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|ClinicalTrials.gov Identifier: NCT03508752|
Recruitment Status : Recruiting
First Posted : April 26, 2018
Last Update Posted : December 8, 2020
|Condition or disease||Intervention/treatment||Phase|
|Brain Metastases||Radiation: Stereotactic Radiosurgery||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/II Trial to Determine the Neurocognitive Decline in Patients With Multiple (>6) Brain Metastases Treated With Distributed Stereotactic Radiosurgery|
|Actual Study Start Date :||December 5, 2017|
|Estimated Primary Completion Date :||December 31, 2023|
|Estimated Study Completion Date :||December 31, 2023|
Radiation: Stereotactic Radiosurgery
Stereotactic Radiosurgery dose is based on the largest tumor size
- Phase I: To determine the toxicity within 60 days from the date of SRS, in patients with a greater intracranial disease burden, defined as 6 or more metastases. [ Time Frame: 60 days ]
Any subject who receives treatment on this protocol will be evaluated for toxicity. Each patient will be assessed for the development of toxicity according to the study calendar. Toxicity will be assessed according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), version 4.0.
The following acute (<30 days) and subacute (>30 days - <60 days) toxicities probably or definitely attributable to the protocol treatment, as defined in CTCAE v4.0, will be dose limiting toxicities (DLT) of the study.
Grade 3 or higher neurologic toxicity in the below categories:
- Symptomatic Central Nervous System Necrosis which is interfering with ADLs (Activities of Daily Living), or requiring treatment with hyperbaric oxygen, Avastin, or resection. Asymptomatic necrosis present on imaging alone does not constitute DLT.
- Cerebral Edema (Grade 4)
- Intracranial Hemorrhage
Any Grade 4 or 5 toxicities definitely attributable to the protocol treatment.
- Phase II: Determine the cognitive deterioration (HVLT delayed recall) in patients treated with SRS for multiple metastases (from baseline to 4 months) [ Time Frame: 4 months ]
The Hopkins Verbal Learning Test (HVLT) is a memory test that gives information about memory.
Each patient will serve as her or his own control, and the relative decline in HVLT-DR (Hopkins Verbal Learning Test- Delayed Recall) score from baseline to 4 month follow-up is deﬁned as
Δ HVLT-DR = (HVLT-R DR at baseline - HVLT-DR at 4 month follow up) / HVLT-DR at baseline.
A positive change indicates a decline in function.
- To determine the optimal dose which will provide local control in patients with a greater intracranial disease burden, defined as 6 or more metastases [ Time Frame: 90 days ]It is assumed that the optimal dose will be the maximum tolerated dose. However, the maximum tolerated dose may or may not be the most ideal dose balancing benefit and toxicity with the widest therapeutic window.
- To determine neurocognitive outcomes [ Time Frame: 3 years ]via HVLT (Hopkins Verbal Learning Test) and quality of life via FACT-Br (Functional Assessment of Cancer Therapy) amongst patients treated with > 6 metastases via SRS.
- To determine overall survival [ Time Frame: 2 years ]overall survival (OS) is defined as the time between date of SRS and date of death
- To determine the time to distant brain recurrence [ Time Frame: 3 years ]distant brain recurrence is defined as time between date of SRS and development of new metastases
- To determine the incidence of salvage WBRT or radiosurgery [ Time Frame: 4 months ]WBRT is defined as whole brain radiation therapy
- To determine the incidence of development of leptomeningeal disease [ Time Frame: 2 years ]Leptomeningeal disease is an exclusion criteria for the study
- To prospectively collect treatment time of patients treated for multiple metastases [ Time Frame: 2 years ]reported in a routine manner at scheduled times during the trial
- Prospectively collect and analyze standard patient demographics [ Time Frame: 3 years ]Patient demographics include age in years, performance status using ECOG (Eastern Cooperative Oncology Group)/Zubrod performance scale, and gender
- Prospectively collect and analyze histology and mutational/hormone status [ Time Frame: 3 years ]Patients' disease status over time
- Prospectively collect and analyze the effect of the type of prior systemic therapy on local control, neurocognitive outcome, quality of life and toxicity [ Time Frame: 3 years ]Prior systemic therapy includes cytotoxic, targeted, or immune therapy
- Prospectively collect and analyze the effect of controlled or uncontrolled systemic disease on local control, neurocognitive outcome, quality of life and toxicity [ Time Frame: 3 years ]How patients are affected by systemic disease over time
- Prospectively collect and analyze neurologic symptoms at the time of SRS [ Time Frame: 3 years ]Symptoms at time of stereotactic radiosurgery
- Prospectively collect and analyze the number of brain metastases and relation to local control, neurocognitive outcome, quality of life, and toxicity [ Time Frame: 3 years ]How the number of brain metastases affects patients' health over time
- Prospectively collect and analyze the size of treated brain metastases [ Time Frame: 3 years ]Measured in millimeters/centimeters
- Prospectively collect and analyze total brain metastases volume and relation to local control, neurocognitive outcome, quality of life, and toxicity [ Time Frame: 3 years ]Total brain metastases volume (cc)
- Prospectively collect and analyze the total treatment time [ Time Frame: 3 years ]Treatment time measured in hours, minutes, and seconds
- Prospectively collect and analyze whole brain integral dose, V8, V10, and V12 and relation to toxicity [ Time Frame: 3 years ]assessed by CTCAE v4.0
- Prospectively collect and analyze hippocampal dose and relation to neurocognitive decline [ Time Frame: 3 years ]Hippocampal dose measured in cGy (centigray); neurocognitive decline assessed by HVLT (Hopkins Verbal Learning Test)
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): NCT03508752
|Contact: Sandra Morones, MSPH||214-645-8525||Sandra.Morones@utsouthwestern.edu|
|Contact: Sarah Hardee, MS||214-685-8525||Sarah.Hardee@utsouthwestern.edu|
|United States, Texas|
|University of Texas Southwestern Medical Center||Recruiting|
|Dallas, Texas, United States, 75390|
|Contact: christian Chukwuma 214-685-8525|
|Principal Investigator:||Zabi Wardak, MD||UT Southwestern Medical Center|