A Phase II Randomized Double-Blind Placebo-Controlled Study of Fisetin to Improve Physical Function in Breast Cancer Survivors
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.
Arms & interventions
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- DrugFisetin
Given PO
- DrugPlacebo Administration
Given PO
- OtherQuality-of-Life Assessment
Ancillary studies
- OtherQuestionnaire Administration
Ancillary studies
Outcome measures
Primary
Change in 6-minute walk distance (6MWD)
The 6MWD is a validated measure of physical function. Participants walk at their own pace for 6 minutes and distance (in meters) is measured at the end. Will be treated as a continuous variable. Its distribution will be transformed to normality as appropriate, Initially, a simple t-test will be used to compare the means of 6MWD at Day 60 by treatment groups.
Time frame: Baseline to day 60
Secondary
Change in grip strength
Time frame: From baseline to day 60
Change in Short Physical Performance Battery score
Time frame: From baseline to day 60
Change in frailty phenotype
Time frame: From baseline to day 60
Change in physical function component of 36-item Short Form (SF-36)
Time frame: From baseline to day 60
Change in the Borg Rating of Perceived Exertion score
Time frame: From baseline to day 60
Change in Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy 20 scores
Time frame: From baseline to day 60
Change in Patient Reported Outcomes Measurement Information System cognitive function short form score
Time frame: From baseline to day 60
Change in composite SF-36 score
Time frame: From baseline to day 60
Change in sleep (Insomnia Severity Index score)
Time frame: From baseline to day 60
Change in anxiety (Generalized Anxiety Disorder-7 score)
Time frame: From baseline to day 60
Change in depression (Patient Health Questionnaire-8 score)
Time frame: From baseline to day 60
Local recurrence free survival
Time frame: Up to 3 years
Distant recurrence free survival
Time frame: Up to 3 years
Breast cancer specific survival and overall survival
Time frame: Up to 3 years
Overall survival
Time frame: Up to 3 years
Adverse events rates
Time frame: Up to 90 days
Adherence rate
Time frame: From baseline up to 30 days
Eligibility criteria
Study locations (7)
UCLA Health Cancer Care in Alhambra
Alhambra, California, 91801
UCLA Health Beverly Hills Primary & Specialty Care
Beverly Hills, California, 90210
UCLA Health Burbank Primary & Specialty Care
Burbank, California, 91505
City of Hope Comprehensive Cancer Center
Duarte, California, 91010
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
UCLA Health Primary Care in Marina del Rey
Marina del Rey, California, 90292
UCLA Health Primary Care in Pasadena
Pasadena, California, 91105
References
- Ji J, Crespi CM, Yee L, Zekster YA, Al-Saleem A, Petersen L, Lee C, Son N, Smith C, Evans T, Tchkonia T, Kirkland JL, Kuchel GA, Cohen HJ, Sedrak MS. A phase II randomized placebo-controlled study of fisetin to improve physical function in breast cancer survivors: the TROFFi study rationale and trial design. Ther Adv Med Oncol. 2026 Mar 11;18:17588359261424668. doi: 10.1177/17588359261424668. eCollection 2026.(PubMed)