Prevention of Frailty with Fisetin and Exercise (PROFFi) in Breast Cancer Survivors

Last updated: December 18, 2024
Sponsor: Jonsson Comprehensive Cancer Center
Overall Status: Active - Recruiting

Phase

2

Condition

N/A

Treatment

Educational Intervention

Biospecimen Collection

Fisetin

Clinical Study ID

NCT06113016
23-001171
P30CA016042
NCI-2023-06774
R01CA280088
  • Female

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Women who are postmenopausal at the start of study treatment

  • Postmenopausal status will be established as follows: Women who are 50 years orolder and who are not menstruating for greater than 12 months will beconsidered postmenopausal. Women who are less than 50 years with an intactuterus and ovaries must have chemically induced menopause (e.g., ovariansuppression) to be considered postmenopausal

  • Women with a diagnosis of early-stage breast cancer (stage I, II, III) treated withneo/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) atbaseline

  • 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 theModification of Diet in Renal Disease (MDRD) calculation

  • Ability to understand and the willingness to sign a written informed consentdocument

Exclusion

Exclusion Criteria:

  • Cancer-directed chemotherapy, biological therapy, or immunotherapy within 30 daysprior 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 medicationadjustment required" may participate if they are otherwise eligible AND themedication can be safely withheld (from immediately before the 1st study agentadministration until at least 10 hours after the last study agentadministration, 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 itsadministration 2 days prior to and during study treatment dosing. Exceptions includecannabidiol (CBD), vitamins, probiotics, and fish oil. Other herbal and naturalmedications 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, lowmolecular weight heparin, factor Xa inhibitors, etc.)

  • Issues with tolerating oral medication (such as but not limited to, inability toswallow pills (gastrostomy [g]-tubes not allowed), malabsorption issues, ongoingnausea 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 thepatient's participation in the clinical study due to safety concerns with clinicalstudy procedures

  • Currently participating in another intervention research study seeking to improvefunctional status, alleviate frailty, muscle strength, exhaustion/fatigue, orcognitive function

Study Design

Total Participants: 164
Treatment Group(s): 8
Primary Treatment: Educational Intervention
Phase: 2
Study Start date:
April 17, 2024
Estimated Completion Date:
August 31, 2031

Study Description

PRIMARY OBJECTIVE:

I. To determine the effect of fisetin and/or exercise on physical function, as assessed using the 6-minute walk distance (6MWD), in chemotherapy-treated postmenopausal breast cancer survivors.

SECONDARY OBJECTIVES:

I. To determine the effect of fisetin and/or exercise on heart rate and step count, as measured by wearable device.

II. To determine the effect of fisetin on other measures of physical function beyond 6MWD (short physical performance battery [SPPB], grip strength, frailty phenotype, physical activity).

III. To determine the effect of fisetin and/or exercise on fatigue (Borg Rating of Perceived Exertion [RPE]).

IV. To determine the effect of fisetin and/or exercise on neuropathy (Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 [QLQ-CIPN20]).

V. To determine the effect of fisetin and/or exercise on cognition (Patient Reported Outcomes Measurement Information System [PROMIS] cognitive function short form).

VI. To determine the effect of fisetin and/or exercise on health-related quality of life (Short Form [SF]-36).

VII. To determine the effect of fisetin on local and distant recurrence free survival (RFS).

VIII. To determine the effect of fisetin on breast cancer-specific survival and overall survival.

IX. To evaluate the safety and tolerability (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]5.0) of fisetin.

X. To estimate rates of adherence to fisetin and/or exercise regimen.

EXPLORATORY OBJECTIVES:

I. To determine the effect of fisetin and/or exercise on p16 expression in peripheral CD3+ T-cells.

II. To determine the effect of fisetin and/or exercise on circulating senescence-associated secretory phenotype (SASP) inflammatory factors in blood and urine.

OUTLINE: Patients are randomized to 1 of 4 arms.

ARM AB: Patients receive fisetin orally (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.

ARM A: 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.

ARM B: 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.

ARM C: 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.

Following completion of study intervention, patients are followed up on days 120 and 180 and then annually for up to 3 years.

Connect with a study center

  • UCLA Health Cancer Care in Alhambra

    Alhambra, California 91801
    United States

    Active - Recruiting

  • UCLA Health Beverly Hills Primary & Specialty Care

    Beverly Hills, California 90210
    United States

    Active - Recruiting

  • UCLA Health Burbank Primary & Specialty Care

    Burbank, California 91505
    United States

    Active - Recruiting

  • UCLA / Jonsson Comprehensive Cancer Center

    Los Angeles, California 90095
    United States

    Active - Recruiting

  • UCLA Health Primary Care in Marina del Rey

    Marina del Rey, California 90292
    United States

    Active - Recruiting

  • UCLA Health Primary Care in Pasadena

    Pasadena, California 91105
    United States

    Active - Recruiting

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.