Neurocognition in Patients With Multiple Brain Metastases Treated With Radiosurgery

Metastatic Malignant Solid Neoplasm Clinical Trial

Official title:

Neurocognition in Patients With Multiple Brain Metastases Treated With Radiosurgery: A Phase II Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03184038
• Other study ID #: 16D.651
• Status: Recruiting
• Phase: Phase 2
• Start date: February 21, 2017
• Est. completion date: September 30, 2025

Study information

• Verified date: November 2023
• Source: Thomas Jefferson University
• Contact: Wenyin Shi, MD
• Phone: (215) 955-6702
• Email: wenyin.shi[@]jefferson.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Neoplasms
• Metastatic Malignant Neoplasm in the Brain
• Metastatic Malignant Solid Neoplasm
• Neoplasms

Intervention

Procedure:
• Cognitive Assessment
Undergo assessment of neurocognitive function

Radiation:
• Stereotactic Radiosurgery
Undergo SRS
• Stereotactic Body Radiation Therapy
Undergo SBRT

Other:
• Quality-of-Life Assessment
Ancillary studies

Locations

Country	Name	City	State
United States	Aria Health	Philadelphia	Pennsylvania
United States	Sidney Kimmel Cancer Center at Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Reading Hospital	Reading	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Sidney Kimmel Cancer Center at Thomas Jefferson University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At 4 months
Secondary	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: ?HVLTi = (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.	Baseline to up to 12 months
Secondary	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.	Baseline to up to 12 months
Secondary	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.	Up to 12 months
Secondary	Local control as measured by magnetic resonance imaging	Will be measured by magnetic resonance imaging.	Up to 12 months
Secondary	Progression free survival (PFS)	Each group will be evaluated using the Kaplan-Meier method.	Up to 12 months
Secondary	Overall survival (OS)	Each group will be evaluated using the Kaplan-Meier method.	Up to 12 months
Secondary	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.	Up to 30 days after SRS

External Links

•   Sidney Kimmel Cancer Center
•   Thomas Jefferson University Hospital