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Assessment of Neurocognitive Function in Patients With Multiple Brain Metastases Undergoing Stereotactic Radiosurgery or Stereotactic Body Radiation Therapy

Primary Purpose

Metastatic Malignant Neoplasm in the Brain, Metastatic Malignant Solid Neoplasm

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Cognitive Assessment
Stereotactic Radiosurgery
Stereotactic Body Radiation Therapy
Quality-of-Life Assessment
Sponsored by
Sidney Kimmel Cancer Center at Thomas Jefferson University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Malignant Neoplasm in the Brain

Eligibility Criteria

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

Inclusion Criteria:

  • Pathologically proven solid tumor malignancy (except for small cell lung cancer [SCLC], germ cell tumor)
  • Karnofsky performance status >= 60
  • 1 to 10 brain metastases (mets) (no more than two lesions and/or cavities >= 3 cm in maximum diameter)
  • Maximum diameter of brain metastasis or resection cavity is 6 cm
  • Serum creatinine =< 3 mg/dL and creatinine clearance >= 30 ml/min
  • Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up; patients must be willing to complete neurocognitive assessments at pre-specified time points outlined in the protocol
  • Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 21 days prior to registration
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 4 months after last dose
  • Patient able to provide his/her own written informed consent and speak English

Exclusion Criteria:

  • Patient with diagnosis of glioma, or other World Health Organization (WHO) grade II - IV primary brain tumor
  • Prior brain surgery =< 14 days prior to enrollment
  • Planned chemotherapy during radiosurgery
  • Leptomeningeal metastases
  • Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per week for the past 2 months
  • Pregnant women

Sites / Locations

  • Sidney Kimmel Cancer Center at Thomas Jefferson UniversityRecruiting
  • Aria Health
  • Reading HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Supportive care (SRS/SBRT, neurocognitive testing)

Arm Description

Patients undergo SRS on day 1 or SBRT for 3 fractions over days 1-7 and undergo neurocognitive testing at baseline, 4, and 12 months after undergoing SRS or SBRT.

Outcomes

Primary Outcome Measures

Neurocognitive function as measured by neurocognitive decline on a battery of tests
The proportion of patients with neurocognitive decline at 4 months post stereotactic radiosurgery (SRS) treatment in each group will be estimated using the sample proportion with the corresponding two-sided 95% confidence interval. The determination of neurocognitive decline will be based on a battery of tests: Hopkins Verbal Learning Test-Revised (HVLT-R) for Total Recall, Delayed Recall, and Delayed Recognition, Controlled Oral Word Association (COWA), and the Trail Making Test (TMT) Parts A and B. The operative definition for neurocognitive decline in this study will be decline on at least one of these measures.

Secondary Outcome Measures

Change in neurocognitive function as measured by neurocognitive decline on a battery of tests conducted by the primary investigator or a trained member of the clinical team
Each patient will serve as his or her own control, and the relative decline in HVLT-R scores from baseline to pre-specified post-treatment internals will be defined as follows: ΔHVLTi = (HVLTB - HVLTF) ÷ HVLTB, where B = baseline and F = follow-up. A positive change indicates a decline in function. Comparison of HVLT-R DR results between control and different time points will be tested using the one-side Wilcoxon signed rank test with significance level of .05. The repeated measures of each neurocognitive test (HVLT-R, COWA, and TMT) and the health-related quality of life (HR-QOL) scale at 2, 4, 6, and 12 months will be analyzed using a linear mixed effects model. The dichotomous indicator of neurocognitive decline based on this battery of tests at 2, 4, 6, and 12 months will be analyzed using a repeated measures logistic regression model.
Change in symptom burden as measured by the MD Anderson Symptom Inventory- Brain Tumor Module (MDASI-BT)
Four subscales (symptom severity, symptom interference, neurologic factor, and cognitive factor score) as well as certain individual items (fatigue, neurologic factor items, and cognitive factor items) of the MDASI-BT will be analyzed. For discrete time point analyses, the change from baseline to each follow-up time point (2, 4, 6, and 12 months from the start of treatment) will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
Quality adjusted survival and health outcomes as measured by the European Quality of Life Five Dimension Five Level scale questionnaire (EQ-5D-5L)
The Z-test will be used to test the hypothesis that the health outcomes in the 2 treatment groups is the same at different time points after initiation of treatment with a significance level of 0.05 and a 2-sided test.
Local control as measured by magnetic resonance imaging
Will be measured by magnetic resonance imaging.
Progression free survival (PFS)
Each group will be evaluated using the Kaplan-Meier method.
Overall survival (OS)
Each group will be evaluated using the Kaplan-Meier method.
Incidence of adverse events graded according to the Common Terminology Criteria for Adverse Events version 5.0
Descriptive analysis will be performed on the acute toxicity data. All estimates of rates (e.g., discontinuation rate and rates of other toxicities) will be presented with corresponding confidence intervals.

Full Information

First Posted
April 5, 2017
Last Updated
September 29, 2023
Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT03184038
Brief Title
Assessment of Neurocognitive Function in Patients With Multiple Brain Metastases Undergoing Stereotactic Radiosurgery or Stereotactic Body Radiation Therapy
Official Title
Neurocognition in Patients With Multiple Brain Metastases Treated With Radiosurgery: A Phase II Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 21, 2017 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
September 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sidney Kimmel Cancer Center at Thomas Jefferson University
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase II trial studies the neurological function in patients with multiple brain metastases undergoing stereotactic radiosurgery (SRS) or stereotactic body radiation therapy (SBRT). Stereotactic body radiation therapy uses special equipment to position a patient and deliver radiation to tumors with high precision. This method can kill tumor cells with fewer doses over a shorter period and cause less damage to normal tissue. Assessment of neurocognitive function may help show that SRS preserves neurological function in patients with multiple brain metastases better than SBRT.
Detailed Description
PRIMARY OBJECTIVES: I. Assessment of neurocognitive function at months 4. SECONDARY OBJECTIVES: I. Assessment of neurocognitive function at months 4 and 12 as measured by neurocognitive decline on a battery of tests. II. Assessment of symptom burden, as measured by the M.D. Anderson Symptom Inventory- Brain Tumor Module (MDASI-BT). III. Assessment of quality adjusted survival and health outcomes using the European Quality of Life Five Dimension Five Level scale questionnaire (EQ-5D-5L). IV. Assessment of local control, in brain control. V. Assessment of progression free survival (PFS), and overall survival (OS). VI. Assessment of side effects and toxicities. OUTLINE: Patients undergo SRS on day 1 or SBRT for 3 fractions over days 1-7 and undergo neurocognitive testing at baseline, 4, and 12 months after undergoing SRS or SBRT. After completion of study, patients are followed up at 2, 4, 6, 8, 10, and 12 months.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Supportive care (SRS/SBRT, neurocognitive testing)
Arm Type
Experimental
Arm Description
Patients undergo SRS on day 1 or SBRT for 3 fractions over days 1-7 and undergo neurocognitive testing at baseline, 4, and 12 months after undergoing SRS or SBRT.
Intervention Type
Procedure
Intervention Name(s)
Cognitive Assessment
Intervention Description
Undergo assessment of neurocognitive function
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
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Other Intervention Name(s)
SBRT, SABR, Stereotactic Ablative Body Radiation Therapy
Intervention Description
Undergo SBRT
Intervention Type
Other
Intervention Name(s)
Quality-of-Life Assessment
Other Intervention Name(s)
Quality of Life Assessment
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Neurocognitive function as measured by neurocognitive decline on a battery of tests
Description
The proportion of patients with neurocognitive decline at 4 months post stereotactic radiosurgery (SRS) treatment in each group will be estimated using the sample proportion with the corresponding two-sided 95% confidence interval. The determination of neurocognitive decline will be based on a battery of tests: Hopkins Verbal Learning Test-Revised (HVLT-R) for Total Recall, Delayed Recall, and Delayed Recognition, Controlled Oral Word Association (COWA), and the Trail Making Test (TMT) Parts A and B. The operative definition for neurocognitive decline in this study will be decline on at least one of these measures.
Time Frame
At 4 months
Secondary Outcome Measure Information:
Title
Change in neurocognitive function as measured by neurocognitive decline on a battery of tests conducted by the primary investigator or a trained member of the clinical team
Description
Each patient will serve as his or her own control, and the relative decline in HVLT-R scores from baseline to pre-specified post-treatment internals will be defined as follows: ΔHVLTi = (HVLTB - HVLTF) ÷ HVLTB, where B = baseline and F = follow-up. A positive change indicates a decline in function. Comparison of HVLT-R DR results between control and different time points will be tested using the one-side Wilcoxon signed rank test with significance level of .05. The repeated measures of each neurocognitive test (HVLT-R, COWA, and TMT) and the health-related quality of life (HR-QOL) scale at 2, 4, 6, and 12 months will be analyzed using a linear mixed effects model. The dichotomous indicator of neurocognitive decline based on this battery of tests at 2, 4, 6, and 12 months will be analyzed using a repeated measures logistic regression model.
Time Frame
Baseline to up to 12 months
Title
Change in symptom burden as measured by the MD Anderson Symptom Inventory- Brain Tumor Module (MDASI-BT)
Description
Four subscales (symptom severity, symptom interference, neurologic factor, and cognitive factor score) as well as certain individual items (fatigue, neurologic factor items, and cognitive factor items) of the MDASI-BT will be analyzed. For discrete time point analyses, the change from baseline to each follow-up time point (2, 4, 6, and 12 months from the start of treatment) will be calculated and compared between treatment arms using a t-test or Wilcoxon-Mann-Whitney test, depending on the normality of the data.
Time Frame
Baseline to up to 12 months
Title
Quality adjusted survival and health outcomes as measured by the European Quality of Life Five Dimension Five Level scale questionnaire (EQ-5D-5L)
Description
The Z-test will be used to test the hypothesis that the health outcomes in the 2 treatment groups is the same at different time points after initiation of treatment with a significance level of 0.05 and a 2-sided test.
Time Frame
Up to 12 months
Title
Local control as measured by magnetic resonance imaging
Description
Will be measured by magnetic resonance imaging.
Time Frame
Up to 12 months
Title
Progression free survival (PFS)
Description
Each group will be evaluated using the Kaplan-Meier method.
Time Frame
Up to 12 months
Title
Overall survival (OS)
Description
Each group will be evaluated using the Kaplan-Meier method.
Time Frame
Up to 12 months
Title
Incidence of adverse events graded according to the Common Terminology Criteria for Adverse Events version 5.0
Description
Descriptive analysis will be performed on the acute toxicity data. All estimates of rates (e.g., discontinuation rate and rates of other toxicities) will be presented with corresponding confidence intervals.
Time Frame
Up to 30 days after SRS

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Pathologically proven solid tumor malignancy (except for small cell lung cancer [SCLC], germ cell tumor) Karnofsky performance status >= 60 1 to 10 brain metastases (mets) (no more than two lesions and/or cavities >= 3 cm in maximum diameter) Maximum diameter of brain metastasis or resection cavity is 6 cm Serum creatinine =< 3 mg/dL and creatinine clearance >= 30 ml/min Patients must have the psychological ability and general health that permits completion of the study requirements and required follow up; patients must be willing to complete neurocognitive assessments at pre-specified time points outlined in the protocol Women of childbearing potential must have a negative beta-human chorionic gonadotropin (HCG) pregnancy test documented within 21 days prior to registration Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for 4 months after last dose Patient able to provide his/her own written informed consent and speak English Exclusion Criteria: Patient with diagnosis of glioma, or other World Health Organization (WHO) grade II - IV primary brain tumor Prior brain surgery =< 14 days prior to enrollment Planned chemotherapy during radiosurgery Leptomeningeal metastases Intractable seizures while on adequate anticonvulsant therapy-more than 1 seizure per week for the past 2 months Pregnant women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wenyin Shi, MD
Phone
(215) 955-6702
Email
wenyin.shi@jefferson.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenyin Shi, MD
Organizational Affiliation
Sidney Kimmel Cancer Center at Thomas Jefferson University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sidney Kimmel Cancer Center at Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenyin Shi, MD
Phone
215-955-6702
Facility Name
Aria Health
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19118
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shari Rudoler, MD
Phone
215-612-4300
First Name & Middle Initial & Last Name & Degree
Shari Rudoler, MD
Facility Name
Reading Hospital
City
Reading
State/Province
Pennsylvania
ZIP/Postal Code
19601
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Terrence Cescon, MD
Phone
484-628-0900

12. IPD Sharing Statement

Links:
URL
https://www.jeffersonhealth.org/clinical-specialties/cancer
Description
Sidney Kimmel Cancer Center
URL
http://hospitals.jefferson.edu/
Description
Thomas Jefferson University Hospital

Learn more about this trial

Assessment of Neurocognitive Function in Patients With Multiple Brain Metastases Undergoing Stereotactic Radiosurgery or Stereotactic Body Radiation Therapy

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