Memantine for Prevention of Cognitive Decline in Patients With Breast Cancer

NCT04033419 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: LCCC19215K12HD001441
• Study Type: interventional
• Target: 55
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Decline; Chemo-brain

Outcome Measures

Primary Outcomes (1)

• Change in Visual Working Memory - Delayed Matching to Sample Test

  The Delayed Matching to Sample Test (DMS) is a computerized cognitive assessment of visual working memory. The DMS will be administered using Cambridge Neuropsychological Test Automated Battery (CANTAB) eclipse software (Cambridge Cognition, Cambridge, UK). The participant is shown an image with four patterns and asked to match patterns simultaneously or after delay. The investigators will use the percent correct (0 to 100, higher is better) at the 12-second delay on the DMS test for the primary analysis.

  From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Secondary Outcomes (16)

• Change in Verbal Memory - Hopkins Verbal Learning Test-Revised

  From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

• Change in Processing Speed and Executive Function - Trail Making Test

  From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

• Change in Processing Speed - Rapid Visual Processing (RVP)

  From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

• Change in Executive Function - One Touch Stockings (OTS) of Cambridge

  From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

• Change in Attention and Working Memory - Digit Span

  From baseline (pre-chemotherapy) to 4 weeks post-chemotherapy

Study Arms (1)

Memantine

EXPERIMENTAL

Subjects receive memantin

Drug: Memantine

Interventions

Memantine DRUG

memantine dose * Week 1: 5 mg dose once daily * Week 2: 5 mg dose twice daily * Week 3: 5 mg each morning/10 mg each evening * Week 4 through the end of Chemotherapy: 10 mg dose twice daily * Total duration: 12 - 26 weeks (depending on chemotherapy regimen)

Also known as: Namenda

Memantine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (1)

• Nakamura ZM, Deal AM, Park EM, Stanton KE, Lopez YE, Quillen LJ, O'Hare Kelly E, Heiling HM, Nyrop KA, Ray EM, Dees EC, Reeder-Hayes KE, Jolly TA, Carey LA, Abdou Y, Olajide OA, Rauch JK, Joseph R, Copeland A, McNamara MA, Ahles TA, Muss HB. A phase II single-arm trial of memantine for prevention of cognitive decline during chemotherapy in patients with early breast cancer: Feasibility, tolerability, acceptability, and preliminary effects. Cancer Med. 2023 Apr;12(7):8172-8183. doi: 10.1002/cam4.5619. Epub 2023 Jan 16.

  PMID: 36645168 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Memantine

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Zev Nakamura, MD
• Organization: University of North Carolina at Chapel Hill, Department of Psychiatry

zev_nakamura@med.unc.edu

(984) 974-3829

Study Officials

• Zev M Nakamura, MD

  Univesity of North Carolina at Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 26, 2019
• Study Start: September 25, 2019
• Primary Completion: April 4, 2022
• Study Completion: April 4, 2022
• Last Updated: April 20, 2023
• Results First Posted: April 20, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 9 to 36 months following publication
• Access Criteria: IRB, IEC, or REB approval, as applicable, and execution of a data use/sharing agreement with UNC.

Locations

US (1)