Trial Title:
Fisetin to Improve Physical Function in Stage I-III Breast Cancer Survivors
NCT ID:
NCT05595499
Condition:
Anatomic Stage I Breast Cancer AJCC V8
Anatomic Stage II Breast Cancer AJCC V8
Anatomic Stage III Breast Cancer AJCC V8
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Arm A (fisetin)
Arm group label:
Arm B (placebo)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Fisetin
Description:
Given PO
Arm group label:
Arm A (fisetin)
Other name:
3,3',4',7-Tetrahydroxyflavone
Other name:
7,3',4'-Flavon-3-ol
Intervention type:
Drug
Intervention name:
Placebo Administration
Description:
Given PO
Arm group label:
Arm B (placebo)
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Arm A (fisetin)
Arm group label:
Arm B (placebo)
Other name:
Quality of Life Assessment
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm A (fisetin)
Arm group label:
Arm B (placebo)
Summary:
This phase II trial tests whether fisetin works to improve physical function in women who
have received chemotherapy for stage I-III breast cancer treatment. Fisetin is a
naturally occurring substance that is found in strawberries and other foods. Fisetin
eliminates cells that have undergone a process called senescence. Senescence is when a
cell ages and permanently stops dividing but does not die. Over time, large numbers of
these cells build up in tissues throughout the body and can release harmful substances
that causes inflammation and damages nearby healthy cells. Studies have shown that
chemotherapy causes a build-up of these senescent cells. Giving fisetin may eliminate
senescent cells and improve physical function in postmenopausal women who have received
chemotherapy for breast cancer.
Detailed description:
PRIMARY OBJECTIVE:
I. To determine the effect of fisetin on physical function, as assessed using the
6-minute walk distance (6MWD), in frail older breast cancer survivors.
SECONDARY OBJECTIVES:
I. To determine the effect of fisetin on other measures of physical function (grip
strength, short physical performance battery [SPPB], frailty phenotype, physical function
component of the 36 item short form survey [SF-36]).
II. To determine the effect of fisetin on fatigability (Borg Rating of Perceived Exertion
[RPE]).
III. To determine the effect of fisetin on neuropathy (Quality of Life Questionnaire -
Chemotherapy-Induced Peripheral Neuropathy 20 [QLQ-CIPN20]).
IV. To determine the effect of fisetin on cognitive function (Patient Reported Outcomes
Measurement Information System [PROMIS] cognitive function short form).
V. To determine the effect of fisetin on health-related quality of life (SF-36).
VI. To determine the effect of fisetin on sleep (Insomnia Severity Index [ISI]).
VII. To determine the effect of fisetin on anxiety (GAD-7). VIII. To determine the effect
of fisetin on depression (PHQ-8). IX. To determine the effect of fisetin on local and
distant recurrence free survival.
X. To determine the effect of fisetin on breast cancer specific survival and overall
survival.
XI. To evaluate the safety and tolerability of fisetin (physician and patient-reported
Common Terminology Criteria for Adverse Events [CTCAEs]).
XII. To estimate rates of adherence to fisetin (pill diary).
EXPLORATORY OBJECTIVES:
I. To determine the effect of fisetin on p16 expression in peripheral CD3+ T-cells.
II. To determine the effect of fisetin on circulating senescence-associated secretory
phenotype (SASP) inflammatory factors.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM A: Patients receive fisetin orally (PO) on days 1, 2, and 3. Treatment repeats every
2 weeks for up to 8 weeks in the absence of disease progression or unacceptable toxicity.
Patients also undergo collection of blood samples throughout the trial.
ARM B: Patients receive placebo PO on the trial. on days 1, 2, and 3. Treatment repeats
every 2 weeks for up to 8 weeks in the absence of disease progression or unacceptable
toxicity. Patients also undergo collection of blood samples throughout the trial.
After completion of study treatment, patients are followed up yearly for up to 3 years.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Women who are postmenopausal at the start of study treatment.
Postmenopausal status will be established as follows:
- Women aged: >= 60 years OR
- Women aged < 60 years AND one of the following conditions is met:
- They have not had any menstrual periods for at least 12 months in the absence
of exogenous hormonal treatments, chemotherapy, and/or tamoxifen AND have serum
estradiol and follicle-stimulating hormone (FSH) levels confirmed as being
within the standard laboratory reference range for postmenopausal females.
- They have documented irreversible bilateral oophorectomy.
- They are receiving ovarian suppression with their breast cancer endocrine
therapy
- Women with a diagnosis of early-stage breast cancer (Stage I-III) treated
with neo/adjuvant chemotherapy within 12 months of starting study
treatment
- No evidence of active/recurrent breast cancer or other serious chronic
illnesses
- Have evidence of frail health, defined as a diminished 6-minute walk
distance (< 400m) at baseline
- Platelets > 60,000/mm^3
- White blood cell count > 2,000/mm^3
- Absolute neutrophil count > 500/mm^3
- Hemoglobin >= 8.0 g/dL
- Total bilirubin =< 3.0 X upper limit of normal (ULN)
- Aspartate aminotransferase (AST) =< 4.0 x ULN
- Alanine aminotransferase (ALT) =< 4.0 x ULN
- Estimated glomerular filtration rate (eGFR) of >= 30mL/min/1.73m^2 per the
Modification of Diet in Renal Disease (MDRD) calculation
- Ability to understand and the willingness to sign a written informed
consent document
Exclusion Criteria:
- Cancer-directed chemotherapy, biological therapy, or immunotherapy within 30 days
prior to the start of study treatment. Exceptions include: trastuzumab, pertuzumab,
pembrolizumab, tamoxifen, and aromatase inhibitors
- Surgery and/or radiation within the last 30 days of starting study treatment
(Exception: invasive non- major procedures such as an outpatient biopsy)
- Subjects taking medications that are considered prohibited.
- Exception: Subjects taking any of the medications listed in under "Temporary
medication adjustment required" may participate if they are otherwise eligible
AND the medication can be safely withheld (from immediately before the 1st
study agent administration until at least 10 hours after the last study agent
administration, for each dosing interval)
- On herbal and natural medications with possible senolytic properties (i.e.,
curcumin, kava kava, St. John's wort) and are unable or unwilling to hold its
administration 2 days prior to and during study treatment dosing. Exceptions include
cannabidiol (CBD), vitamins, probiotics, and fish oil. Other herbal and natural
medications may be permitted or prohibited per clinician discretion
- Subjects taking potentially senolytic agents within the last year: fisetin,
quercetin, luteolin, dasatinib or imatinib (or other tyrosine kinase inhibitors),
piperlongumine, or navitoclax
- Subjects on therapeutic doses of anticoagulants (e.g., warfarin, heparin, low
molecular weight heparin, factor Xa inhibitors, etc.)
- Issues with tolerating oral medication (such as but not limited to, inability to
swallow pills (g-tubes not allowed), malabsorption issues, ongoing nausea or
vomiting during screening, history of Crohn's, gastric bypass/reduction, or celiac
disease)
- Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns with clinical
study procedures
- Currently participating in another intervention research study seeking to improve
functional status, alleviate frailty, muscle strength, exhaustion/fatigue, or
cognitive function
Gender:
Female
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
City of Hope Comprehensive Cancer Center
Address:
City:
Duarte
Zip:
91010
Country:
United States
Status:
Recruiting
Contact:
Last name:
Marie Bae
Phone:
626-256-4673
Phone ext:
85200
Email:
mbae@coh.org
Contact backup:
Last name:
Marie D. Yee, MD
Phone:
626-256-4673
Phone ext:
85200
Email:
lyee@coh.org
Contact backup:
Last name:
Lisa D. Yee, MD
Facility:
Name:
UCLA / Jonsson Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mina S. Sedrak
Phone:
310-825-3181
Email:
msedrak@mednet.ucla.edu
Contact backup:
Last name:
Mina S. Sedrak
Start date:
March 27, 2023
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Jonsson Comprehensive Cancer Center
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
National Institute on Aging (NIA)
Agency class:
NIH
Source:
Jonsson Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05595499
