Clinical trial NCT04033419: Memantine for Prevention of Cognitive Decline in Patients With Breast Cancer
Official title: Memantine for Prevention of Cognitive Decline During Adjuvant or Neoadjuvant Chemotherapy in Patients With Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cognitive Decline
Chemo-brain
Lead sponsor: UNC Lineberger Comprehensive Cancer Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2019-07-26
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: Purpose: To conduct a one-arm phase II trial to: (1) compare changes in pre- to post-chemotherapy cognitive function in a cohort of patients with breast cancer receiving memantine to historical controls; (2) examine how depression, anxiety, fatigue, baseline Intelligence Quotient (IQ), and cognitive effort relate to objective and self-reported cognitive function; and (3) estimate the feasibility of conducting a clinical trial of memantine for attenuating cognitive decline in patients with breast cancer during chemotherapy.

Participants: Adult patients with stage I-III breast cancer scheduled for adjuvant or neoadjuvant chemotherapy.

Procedures (methods): Cognitive assessments will be performed within one week of initiating and four weeks after completion of chemotherapy. Patients will receive memantine 10 mg twice daily between the pre- and post-chemotherapy study assessments. Cognitive function will be assessed objectively using a computerized cognitive test (Delayed Matching to Sample (DMS) test) and a standard neuropsychological battery. To assess subjective cognitive function, the Patient Reported Outcome Measurement Information System (PROMIS) Cognitive Function measure will be used. Depression, anxiety, fatigue, menopausal status, and sleep will be assessed as covariates.

Detailed description: This is a one-arm phase II interventional study in patients with breast cancer to investigate whether memantine can prevent cognitive decline during chemotherapy. The investigators will recruit 56 participants referred to the University of North Carolina (UNC) Breast Center and affiliated outpatient clinics for initiation of adjuvant or neoadjuvant chemotherapy, perform a cognitive assessment within one week of initiating and four weeks after completion of chemotherapy, and treat with memantine 10 mg twice daily between the pre- and post-chemotherapy study assessments (estimated duration: 12-26 weeks, depending on the chemotherapy regimen). Cognitive function will be assessed objectively using a computerized cognitive assessment (Delayed Matching to Sample (DMS) test) and a standard neuropsychological battery. To assess subjective cognitive function, the Patient Reported Outcome Measurement Information System (PROMIS) Cognitive Function measure will be used. Depression, anxiety, fatigue, menopausal status, and sleep are comorbidities known to affect cognitive function, and therefore will be assessed as covariates pre- and post-chemotherapy. Depression, anxiety, health-related quality of life (HRQOL) and functional status will be evaluated as secondary outcomes. The feasibility of the investigator's study by monitoring recruitment, retention, and adherence to memantine will be assessed.

Eligibility criteria: Inclusion Criteria:

* Able to provide informed consent
* At least 18 years of age
* Able to speak English
* Diagnosed with breast cancer, Stages I-III
* Scheduled for adjuvant or neoadjuvant chemotherapy

Exclusion Criteria:

* A history of adverse reaction to memantine
* Another cancer diagnosis with an estimated survival of less than five years
* Previous chemotherapy exposure
* Severe cognitive impairment, defined as Blessed Orientation Memory Concentration Test (BOMC) ≥ 11.
* Pregnancy, confirmed by a negative pregnancy test within 30 days of study enrollment, or breastfeeding
* Current alcohol or drug abuse

Primary outcomes:
measure: Change in Visual Working Memory - Delayed Matching to Sample Test
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
Secondary outcomes:
measure: Change in Verbal Memory - Hopkins Verbal Learning Test-Revised
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Processing Speed and Executive Function - Trail Making Test
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Processing Speed - Rapid Visual Processing (RVP)
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Executive Function - One Touch Stockings (OTS) of Cambridge
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Attention and Working Memory - Digit Span
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Verbal Fluency - Controlled Oral Word Association Test
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Semantic Fluency - Animal Naming Test
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Self-reported Cognitive Function - PROMIS Cognitive Function
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Depressive Symptoms - PROMIS Depression
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Anxiety Symptoms - PROMIS Emotional Distress-Anxiety
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy.
measure: Change in Karnofsky Performance Status
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Change in Quality of Life - Functional Assessment of Cancer Therapy-General
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Proportion of Invited Participants Who Enroll - Recruitment
timeFrame: Baseline (pre-chemotherapy) over the duration of the accrual period
measure: Proportion of Enrolled Participants Who do Not Meet the Primary Outcome Measure - Attrition
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Proportion of Scheduled Drug Doses Taken - Adherence
timeFrame: From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy
measure: Number of Adverse Events - Safety
timeFrame: From baseline to 4 weeks after chemotherapy (up to 30 weeks)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: Univesity of North Carolina at Chapel Hill
name: Zev M Nakamura, MD
role: PRINCIPAL_INVESTIGATOR
References: