Study of Donepezil in Female Breast Cancer Survivors With Cognitive Dysfunction

Sponsor
Wake Forest University Health Sciences (Other)
Overall Status
Completed
CT.gov ID
NCT01466270
Collaborator
National Cancer Institute (NCI) (NIH)
62
2
15

Study Details

Study Description

Brief Summary

RATIONALE: Donepezil hydrochloride may help lessen cognitive dysfunction caused by chemotherapy.

PURPOSE: This phase II trial is studying donepezil hydrochloride in treating cognitive dysfunction after chemotherapy in female breast cancer survivors.

Condition or Disease Intervention/Treatment Phase
  • Drug: donepezil hydrochloride
  • Drug: Placebo
Phase 2

Detailed Description

OBJECTIVES:

Primary

  • Determine the feasibility of conducting a randomized placebo-controlled clinical trial for cognitive symptoms in female breast cancer survivors.

Secondary

  • Estimate the variability of the clinical outcomes (FACT-Cognition Perceived Cognitive Impairment subscale, neurocognitive battery, FACIT-Fatigue, FACT Cog Total Score, PROMIS Fatigue, Epworth Sleepiness Scale, Beck Depression Inventory, Beck Anxiety Inventory, and RAND Short Form-36).

  • Estimate the within patient correlation over time of the clinical outcomes.

  • Obtain preliminary estimates of the effect of donepezil on the primary and secondary outcome variables.

  • Correlate the reports of fatigue, sleep disturbance, and mood with measures of cognitive symptoms and neurocognitive test performance.

  • Document the severity of cognitive symptoms and functional impairment in female breast cancer survivors who enroll on this pilot study.

  • Correlate cognitive symptoms with cognitive test performance.

  • Document the toxicities associated with donepezil hydrochloride use.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to menopausal status (pre- vs peri-/post-menopausal) and time since end of chemotherapy (12-36 months vs 36.01-60 months).

Arm I: Patients receive donepezil hydrochloride orally (PO) once daily (QD).

Arm II: Patients receive placebo PO QD.

In both arms treatment continues for 24 weeks.

Patients complete the entire battery of neurocognitive tests and questionnaires (FACT-Cognition Perceived Cognitive Impairment subscale, neurocognitive battery, FACIT-Fatigue, FACT Cog Total Score, PROMIS Fatigue, Epworth Sleepiness Scale, Beck Depression Inventory, Beck Anxiety Inventory, and RAND Short Form-36) at baseline (pre-treatment), 24 weeks (end of medication), and 36 weeks (end of wash-out).

After completion of therapy, patients are followed at 12 weeks.

Study Design

Study Type:
Interventional
Actual Enrollment :
62 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Feasibility Study of Donepezil in Female Breast Cancer Survivors With Self-Reported Cognitive Dysfunction Following Chemotherapy
Actual Study Start Date :
Jul 1, 2012
Actual Primary Completion Date :
Oct 1, 2013
Actual Study Completion Date :
Oct 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm I

Patients receive donepezil hydrochloride PO QD.

Drug: donepezil hydrochloride
Given PO
Other Names:
  • Donepezil
  • Placebo Comparator: Arm II

    Patients receive placebo PO QD.

    Drug: Placebo
    Given PO

    Outcome Measures

    Primary Outcome Measures

    1. Retention [24 Weeks]

      Retention is the percentage of participants who stay in the study for 24 weeks.

    2. Compliance [24 weeks]

      Compliance is the percentage of pills taken while on study (based on returned diaries)

    Secondary Outcome Measures

    1. HVLT-IR [24 weeks]

      Hopkins verbal learning test - immediate recall is the number of words (of 12) than can be remembers during three tries. The total score ranges from 0 to 36. Higher is better.

    2. Fatigue [24 weeks]

      Fatigue is quantified by the FACIT-Fatigue scale. It consists of 13 questions answered on a 0 to 4 point scale. The fatigue score is the sum of the responses (some reverse scored) so that higher values represent less fatigue.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    INCLUSION CRITERIA:
    • Adults >18 years old.

    • Female with history of invasive breast cancer

    • Must have completed adjuvant chemotherapy between 1 and 5 years prior to registration

    • Received at least 4 cycles of cytotoxic chemotherapy

    • Documentation of prior chemotherapy

    • Patients receiving ongoing hormonal therapy for breast cancer must be on the same hormonal agent for at least 3 months prior to study registration and continue for the duration of the study (9 months)

    • Karnofsky Performance Status must be > 60 or ECOG 0-2.

    • Use of psychotropic medications (anti-depressants, anxiolytics, sleeping aids, narcotics) is permitted. Patient will be asked to list any that have been taken within the last 3 days on the recent medication sheet.

    • Patients must be able to give informed consent to participate in the study, including signing the consent form.

    • Self-reported cognitive disruption (FACT-Cog Version 3 Perceived Cognitive Impairments sub-score of < 63)

    • Negative serum pregnancy test within 10 days prior to registration for women of child-bearing potential.

    EXCLUSION CRITERIA:
    • Evidence or suspected recurrent or metastatic disease

    • History of dementia, Alzheimer's disease, multi-infarct dementia or CVA (history of transient ischemic attack (TIA is allowed)

    • Current use of donepezil, galantamine, rivastigmine, tacrine, memantine, methylphenidate, dextroamphetamine, or any other specific cognition enhancing drugs.are not allowed. For patients who have used these medications they must not have used them within 4 weeks prior to registration.

    Patients may not currently be taking Ketoconazole or Quinidine

    • Hypersensitivity to donepezil.

    • Use of investigational medications within the last 30 days.

    • Prior brain metastasis

    • Traumatic brain injury, multiple sclerosis or recent myocardial infarction

    • History of schizophrenia, psychosis or substance abuse

    • Untreated current severe depression. (Currently treated depression is permitted if treatment is stable.)

    • Acute severe fatigue, chronic fatigue syndrome or fibromyalgia.

    • History of hepatic or renal dysfunction or disease

    • Pregnant women are excluded from this study. The effects of donepezil on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because donepezil is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately.

    • It is unknown whether donepezil is excreted in breast milk, for this reason women who are currently breast-feeding are not eligible for this study.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • Wake Forest University Health Sciences
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Julia A. Lawrence, Wake Forest University Health Sciences

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT01466270
    Other Study ID Numbers:
    • IRB00019792-1
    • U10CA081851
    • REBACCCWFU 97211
    First Posted:
    Nov 6, 2011
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Sep 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Wake Forest University Health Sciences
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Patients were accrued between 7/12 and 1/13 from CCOP sites across the nation.
    Pre-assignment Detail No wash-out or run-in period. All enrolled patients were randomized.
    Arm/Group Title Arm I - Donepezil Arm II - Placebo
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. Patients receive placebo PO QD.
    Period Title: Overall Study
    STARTED 31 31
    COMPLETED 19 25
    NOT COMPLETED 12 6

    Baseline Characteristics

    Arm/Group Title Arm I - Donepezil Arm II - Placebo Total
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. Patients receive placebo PO QD. Total of all reporting groups
    Overall Participants 31 31 62
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    24
    77.4%
    27
    87.1%
    51
    82.3%
    >=65 years
    7
    22.6%
    4
    12.9%
    11
    17.7%
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    56
    56
    56
    Sex: Female, Male (Count of Participants)
    Female
    31
    100%
    31
    100%
    62
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    31
    100%
    31
    100%
    62
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    4
    12.9%
    1
    3.2%
    5
    8.1%
    White
    27
    87.1%
    29
    93.5%
    56
    90.3%
    More than one race
    0
    0%
    1
    3.2%
    1
    1.6%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    31
    100%
    31
    100%
    62
    100%

    Outcome Measures

    1. Primary Outcome
    Title Retention
    Description Retention is the percentage of participants who stay in the study for 24 weeks.
    Time Frame 24 Weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized patients
    Arm/Group Title Arm I Arm II
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. donepezil hydrochloride: Given PO Patients receive placebo PO QD. Placebo: Given PO
    Measure Participants 31 31
    Mean (Standard Error) [percentage of participants]
    71.0
    (8.3) 229%
    80.7
    (7.2) 260.3%
    2. Primary Outcome
    Title Compliance
    Description Compliance is the percentage of pills taken while on study (based on returned diaries)
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    Participants who returned pill diaries. Note that some participants did not return diaries so the numbers of participants for this analysis may not agree with the numbers for other analyses.
    Arm/Group Title Arm I - Donepezil Arm II - Placebo
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. Patients receive placebo PO QD.
    Measure Participants 26 27
    Mean (Full Range) [percentage of pills]
    98.0
    98.0
    3. Secondary Outcome
    Title HVLT-IR
    Description Hopkins verbal learning test - immediate recall is the number of words (of 12) than can be remembers during three tries. The total score ranges from 0 to 36. Higher is better.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants except two who did not provide any data.
    Arm/Group Title Arm I - Donepezil Arm II - Placebo
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. Patients receive placebo PO QD.
    Measure Participants 30 30
    Least Squares Mean (Standard Error) [number of words recalled]
    25.58
    (1.36)
    22.94
    (1.24)
    4. Secondary Outcome
    Title Fatigue
    Description Fatigue is quantified by the FACIT-Fatigue scale. It consists of 13 questions answered on a 0 to 4 point scale. The fatigue score is the sum of the responses (some reverse scored) so that higher values represent less fatigue.
    Time Frame 24 weeks

    Outcome Measure Data

    Analysis Population Description
    All randomized participants except two who did not provide any data.
    Arm/Group Title Arm I - Donepezil Arm II - Placebo
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. Patients receive placebo PO QD.
    Measure Participants 30 30
    Least Squares Mean (Standard Error) [units on a scale]
    35.89
    (2.20)
    35.51
    (2.02)

    Adverse Events

    Time Frame 40 weeks (one month following the end of the study)
    Adverse Event Reporting Description The numbers of participants for this analysis may not agree with the numbers for the other analyses as not all participants completed their AE/toxicity evaluations.
    Arm/Group Title Arm I - Donepezil Arm II - Placebo
    Arm/Group Description Patients receive donepezil hydrochloride PO QD. Patients receive placebo PO QD.
    All Cause Mortality
    Arm I - Donepezil Arm II - Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Arm I - Donepezil Arm II - Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/28 (7.1%) 1/30 (3.3%)
    General disorders
    Insomnia 2/28 (7.1%) 3 0/30 (0%) 0
    Pain: Chest Wall 0/28 (0%) 0 1/30 (3.3%) 1
    Musculoskeletal and connective tissue disorders
    Muscle Cramps 0/28 (0%) 0 1/30 (3.3%) 2
    Nervous system disorders
    Headache 1/28 (3.6%) 1 0/30 (0%) 0
    Other (Not Including Serious) Adverse Events
    Arm I - Donepezil Arm II - Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 28/28 (100%) 30/30 (100%)
    Gastrointestinal disorders
    Diarrhea 7/28 (25%) 11 6/30 (20%) 9
    Nausea 8/28 (28.6%) 10 8/30 (26.7%) 12
    General disorders
    Anorexia 4/28 (14.3%) 5 7/30 (23.3%) 11
    Fatigue 20/28 (71.4%) 49 19/30 (63.3%) 49
    Insomnia 18/28 (64.3%) 37 21/30 (70%) 49
    Musculoskeletal and connective tissue disorders
    Muscle Cramps 15/28 (53.6%) 29 8/30 (26.7%) 14
    Pain: joint 0/28 (0%) 0 2/30 (6.7%) 2
    Nervous system disorders
    Cognitive Disturbance 2/28 (7.1%) 2 0/30 (0%) 0
    Headache 11/28 (39.3%) 15 8/30 (26.7%) 15
    Neuropathy: sensory 3/28 (10.7%) 5 2/30 (6.7%) 3

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Doug Case
    Organization Wake Forest School of Medicine
    Phone 336-716-1048
    Email dcase@wakehealth.edu
    Responsible Party:
    Wake Forest University Health Sciences
    ClinicalTrials.gov Identifier:
    NCT01466270
    Other Study ID Numbers:
    • IRB00019792-1
    • U10CA081851
    • REBACCCWFU 97211
    First Posted:
    Nov 6, 2011
    Last Update Posted:
    Oct 20, 2021
    Last Verified:
    Sep 1, 2021