Prevention of Frailty With Fisetin and Exercise in Breast Cancer Survivors

NCT06113016 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: 23-001171P30CA016042R01CA280088NCI-2023-06774
• Study Type: interventional
• Target: 164
• Locations: 1 country
• Sites: 6

Brief Summary

This phase II trial tests how well fisetin and exercise works in preventing frailty in breast cancer survivors. Fisetin is a natural substance found in strawberries and other foods and is available as a nutritional supplement. Nutritional supplements may be useful in eliminating 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 cause inflammation and damage nearby healthy cells. Giving fisetin may eliminate senescent cells in patients with breast cancer undergoing physical activity.

Conditions

Anatomic Stage I Breast Cancer American Joint Committee on Cancer (AJCC) v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Early Stage Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Change in 6 minute walk distance (6MWD)

  The 6MWD will assess the distance walked over 6 minutes and is measured in meters. A linear model will be fit to outcome variable (change score) with a factor variable representing the four study arms and control for baseline 6MWD, site, and age stratum. The analysis will be conducted as intention-to-treat analysis. Will conduct an as-treated analysis, comparing the treatments received (instead of as-randomized).

  From baseline to day 120

Secondary Outcomes (15)

• Change in heart rate

  From baseline to day 120

• Change in step count

  From baseline to day 120

• Change in short physical performance battery (SPPB)

  From baseline to day 120

• Change in grip strength

  From baseline to day 120

• Change in frailty phenotype

  From baseline to day 120

Study Arms (4)

Arm A (fisetin, physical activity handout)

ACTIVE COMPARATOR

Patients receive fisetin PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive handout on the importance of physical activity during baseline. Patients undergo collection of blood samples on study.

Procedure: Biospecimen Collection; Other: Educational Intervention; Drug: Fisetin; Other: Physical Performance Testing; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm AB (fisetin, tailored exercise training)

EXPERIMENTAL

Patients receive fisetin PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive individually tailored supervised exercise training consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training three times a week over 16 weeks. Patients undergo collection of blood samples on study.

Procedure: Biospecimen Collection; Other: Exercise Intervention; Drug: Fisetin; Other: Physical Performance Testing; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm B (placebo, tailored exercise training)

ACTIVE COMPARATOR

Patients receive placebo PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive individually tailored supervised exercise training consisting of 30-45 minutes of aerobic training and 20-30 minutes of resistance training three times a week over 16 weeks. Patients undergo collection of blood samples on study.

Procedure: Biospecimen Collection; Other: Exercise Intervention; Other: Physical Performance Testing; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm C (placebo, physical activity handout)

ACTIVE COMPARATOR

Patients receive placebo PO on days 1-3 of each cycle. Treatment repeats every 14 days for 8 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive handout on the importance of physical activity during baseline. Patients undergo collection of blood samples on study.

Procedure: Biospecimen Collection; Other: Educational Intervention; Other: Physical Performance Testing; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm A (fisetin, physical activity handout); Arm AB (fisetin, tailored exercise training); Arm B (placebo, tailored exercise training); Arm C (placebo, physical activity handout)

Educational Intervention OTHER

Receive handout on physical activity

Also known as: Education for Intervention, Intervention by Education, Intervention through Education, Intervention, Educational

Arm A (fisetin, physical activity handout); Arm C (placebo, physical activity handout)

Exercise Intervention OTHER

Receive individually tailored exercise intervention

Arm AB (fisetin, tailored exercise training); Arm B (placebo, tailored exercise training)

Fisetin DRUG

Given PO

Also known as: 3,3',4',7-Tetrahydroxyflavone, 7,3',4'-Flavon-3-ol

Arm A (fisetin, physical activity handout); Arm AB (fisetin, tailored exercise training)

Physical Performance Testing OTHER

Ancillary studies

Also known as: Physical Fitness Testing, Physical Function Testing

Arm A (fisetin, physical activity handout); Arm AB (fisetin, tailored exercise training); Arm B (placebo, tailored exercise training); Arm C (placebo, physical activity handout)

Placebo Administration DRUG

Given PO

Arm B (placebo, tailored exercise training); Arm C (placebo, physical activity handout)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm A (fisetin, physical activity handout); Arm AB (fisetin, tailored exercise training); Arm B (placebo, tailored exercise training); Arm C (placebo, physical activity handout)

Questionnaire Administration OTHER

Ancillary studies

Arm A (fisetin, physical activity handout); Arm AB (fisetin, tailored exercise training); Arm B (placebo, tailored exercise training); Arm C (placebo, physical activity handout)

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Women who are postmenopausal at the start of study treatment
• Postmenopausal status will be established as follows: Women who are 50 years or older and who are not menstruating for greater than 12 months will be considered postmenopausal. Women who are less than 50 years with an intact uterus and ovaries must have chemically induced menopause (e.g., ovarian suppression) to be considered postmenopausal
• Women with a diagnosis of early-stage breast cancer (stage I, II, 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 pre-frail health, defined as a 6-minute walk distance (400-480m) 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. GFR (mL/min/1.73 m²) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
• Ability to understand and the willingness to sign a written informed consent document

You may not qualify if:

• 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 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 (gastrostomy \[g\]-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

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator
• Rising Tide Foundation: collaborator

Study Sites (6)

UCLA Health Cancer Care in Alhambra

Alhambra, California, 91801, United States

RECRUITING

UCLA Health Beverly Hills Primary & Specialty Care

Beverly Hills, California, 90210, United States

RECRUITING

UCLA Health Burbank Primary & Specialty Care

Burbank, California, 91505, United States

RECRUITING

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

RECRUITING

UCLA Health Primary Care in Marina del Rey

Marina del Rey, California, 90292, United States

RECRUITING

UCLA Health Primary Care in Pasadena

Pasadena, California, 91105, United States

RECRUITING

MeSH Terms

Interventions

Specimen Handling; Early Intervention, Educational; Educational Status; Methods; fisetin; Exercise Test

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Child Health Services; Community Health Services; Health Services; Health Care Facilities Workforce and Services; Preventive Health Services; Socioeconomic Factors; Population Characteristics; Heart Function Tests; Diagnostic Techniques, Cardiovascular; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry

Study Officials

• Mina S Sedrak

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mina S. Sedrak, MD

CONTACT

310-825-3181; msedrak@mednet.ucla.edu

Kelly Synold

CONTACT

424-440-3877; ksynold@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This is a double-blind study with respect to study agent. Because participants cannot be blinded to exercise training, the outcomes assessor (but not the physicians or participants) will be blinded to the training status of participants.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2023
• First Posted: November 2, 2023
• Study Start: July 23, 2024
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: July 8, 2025

Record last verified: 2025-06

Locations

US (6)