Page 11 - Delaware Medical Journal - November/December 2018

CANCER CLINICAL TRIAL
PROTOCOL OF THE MONTH
WF 97116: Phase 3 Randomized Placebo-Controlled Clinical Trial of Donepezil in Chemotherapy Exposed
Breast Cancer Survivors with Cognitive Impairment
The objectives of the trial are:
Primary Objective:
Aim 1: Determine whether randomization to a 24-week course of treatment with donepezil compared to placebo improves memory performance in women who have received chemotherapy for breast cancer 1 to 5 years previously. Hypothesis: Women randomized to donepezil for 24 weeks will have better memory performance than women receiving placebo.
Secondary Objective:
Aim 2: Determine whether a 24-week course of treatment with donepezil compared to placebo improves executive functions (working memory, verbal fluency, set shifting), processing speed and global cognitive performance in women who have received chemotherapy for breast cancer 1 to 5 years previously. Hypothesis: Women randomized to donepezil for 24 weeks will have better executive function, processing speed and global cognitive performance than women receiving placebo.
Aim 3: Determine if a 24-week course of treatment with donepezil reduces self-reported cognitive problems in women who have received chemotherapy for breast cancer 1 to 5 years previously compared to placebo. Hypothesis: Women randomized to donepezil for 24 weeks will report fewer cognitive problems than women receiving placebo.
Aim 4: To determine the effect of a 24-week course of treatment with donepezil on toxicities and adverse events. Hypothesis: No group difference. Tertiary (Exploratory) Objectives:
Aim 5: Determine whether APOE genotype (1 or 2, 4 alleles v none) is associated with poorer pre-randomization cognitive performance and more cognitive complaints in women who have received chemotherapy for breast cancer 1 to 5 years previously and to determine if APOE predicts who will respond to treatment. Hypothesis: Women who are carriers of the APOE 4 alleles will have poorer pre-randomization cognitive performance, more cognitive complaints, and respond better to donepezil than women without the 4 alleles.
Aim 6: Determine whether low cognitive reserve (CR) is associated with poorer pre-randomization cognitive performance and more cognitive complaints in women who have received chemotherapy for breast cancer 1 to 5 years previously and determine if cognitive reserve predicts who will respond to treatment. Hypothesis: Women with lower CR will have poorer pre-randomization cognitive performance, more cognitive complaints, and respond better to donepezil than women high in CR.
Eligibility
• Must be able to speak English.
• Women ≥18 years old with history of invasive breast cancer and ECOG performance status 0-2.
• Must have completed at least 4 cycles of adjuvant/neo-adjuvant cytotoxic chemotherapy between 1 and 5 years prior to enrollment (Ongoing herceptin or other chronic HER 2 directed therapies are allowed).
• Patients receiving ongoing hormonal therapy for breast cancer must be on the same hormonal agent for at least 3 months prior to study enrollment and plan to continue for the duration of the study (9 months).
• 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) if dose is stable over previous 12 weeks.
• Self-reported cognitive problem plus a measured memory deficit (score <7 on single trial of Eligibility Pre-screen HVLT-R Form C).
Treatment: Donepezil or placebo will be taken once daily by mouth.
Weeks 1-6 one 5 mg tablet of donepezil or one matching placebo tablet orally once a day
THEN TITRATE TO
Weeks 7-24 two 5 mg tablets of donepezil (10 mg total) or 2 tablets of matching placebo orally once a day.
For information regarding this clinical trial or if you would like to have the list of open protocols emailed to you, please call the Cancer Research Office at (302) 623-4450 or email akee@christianacare.org.
Del Med J | November/December 2018 | Vol. 90 | No. 8 279