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RecruitingInterventionalPhase 2

A Phase II Randomized Double-Blind Placebo-Controlled Study of Fisetin to Improve Physical Function in Breast Cancer Survivors

NCT ID: NCT05595499Sponsor: Jonsson Comprehensive Cancer CenterLast updated: 2025-07-02

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

Sex: FemaleAge: All agesHealthy volunteers: No
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, ribociclib, abemaciclib, aromatase inhibitors and/or ovarian suppression. * 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

Study locations (7)

UCLA Health Cancer Care in Alhambra

Alhambra, California, 91801

Recruiting
Mina S. Sedrak, MD · Contact

UCLA Health Beverly Hills Primary & Specialty Care

Beverly Hills, California, 90210

Recruiting
Mina S. Sedrak, MD · Contact

UCLA Health Burbank Primary & Specialty Care

Burbank, California, 91505

Recruiting
Mina S. Sedrak, MD · Contact

City of Hope Comprehensive Cancer Center

Duarte, California, 91010

Recruiting
Keilani Luna · Contact
Marie D. Yee, MD · Contact
Lisa D. Yee, MD · Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095

Recruiting
Mina S. Sedrak · Contact
Mina S. Sedrak · Principal Investigator

UCLA Health Primary Care in Marina del Rey

Marina del Rey, California, 90292

Recruiting
Mina S. Sedrak, MD · Contact

UCLA Health Primary Care in Pasadena

Pasadena, California, 91105

Recruiting
Mina S. Sedrak, MD · Contact

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)