Anatomic Stage I Breast Cancer American Joint Committee on Cancer (AJCC) v8Phase 2PROFFiNCT06113016
Prevention of Frailty With Fisetin and Exercise in Breast Cancer Survivors
A Phase 2 study testing Biospecimen Collection, Educational Intervention and Exercise Intervention in people with Anatomic Stage I Breast Cancer American Joint Committee on Cancer (AJCC) v8 and Anatomic Stage II Breast Cancer AJCC v8, run by Jonsson Comprehensive Cancer Center at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- 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
- What is being tested?
- Biospecimen Collection, Educational Intervention and Exercise Intervention
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 164 participants
- Where
- 6 sitesUnited States
- Study dates
- 23 Jul 2024to 31 Oct 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
6 sites in 1 country. Contact the study team or a site near you to ask about taking part.
6 sites in 1 country
United States6 sites, 6 recruiting
- Recruiting
UCLA Health Cancer Care in Alhambra
Alhambra, California, 91801
Mina S. Sedrak, MD, 310-825-3181, msedrak@mednet.ucla.edu
- Recruiting
UCLA Health Beverly Hills Primary & Specialty Care
Beverly Hills, California, 90210
Mina S. Sedrak, MD, 310-825-3181, msedrak@mednet.ucla.edu
- Recruiting
UCLA Health Burbank Primary & Specialty Care
Burbank, California, 91505
Mina S. Sedrak, MD, 310-8253181, msedrak@mednet.ucla.edu
- Recruiting
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
Mina S. Sedrak, 310-825-3181, msedrak@mednet.ucla.edu
Mina S. Sedrak
- Recruiting
UCLA Health Primary Care in Marina del Rey
Marina del Rey, California, 90292
Mina S. sedrak, MD, 310-825-3181, msedrak@mednet.ucla.edu
- Recruiting
UCLA Health Primary Care in Pasadena
Pasadena, California, 91105
Mina S. Sedrak, MD, 310-825-3181, msedrak@mednet.ucla.edu
About this study
Official title: A Phase II Randomized Placebo-Controlled Study of Fisetin and Exercise to Prevent Frailty in Breast Cancer Survivors
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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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]).
- 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.
- To estimate rates of adherence to fisetin and/or exercise regimen.
EXPLORATORY OBJECTIVES:
- 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.
- 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
- Being tested
- Biospecimen Collection, Educational Intervention, Exercise Intervention, Fisetin, Physical Performance Testing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection
Undergo collection of blood samples
Educational InterventionOther
Also called Education for Intervention, Intervention by Education, Intervention through Education, Intervention, Educational
Receive handout on physical activity
Exercise InterventionOther
Receive individually tailored exercise intervention
FisetinDrug
Also called 3,3',4',7-Tetrahydroxyflavone, 7,3',4'-Flavon-3-ol
Given PO
Physical Performance TestingOther
Also called Physical Fitness Testing, Physical Function Testing
Ancillary studies
Placebo AdministrationDrug
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Procedure: Biospecimen Collection; Other: Educational Intervention; Other: Physical Performance Testing; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From baseline to day 120
Secondary outcomes (15)
Change in heart rate
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in step count
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in short physical performance battery (SPPB)
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in grip strength
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in frailty phenotype
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in physical function subsection of Short Form (SF)-36
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in the Borg Rating of Perceived Exertion (RPE)
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends.
Measured: From baseline to day 120
Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) scores
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends. Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20). Scoring range is from 20-80. A lower score defines a more favorable outcome.
Measured: From baseline to day 120
Change in Patient Reported Outcomes Measurement Information System (PROMIS) cognitive function short form score
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends. Patient Reported Outcomes Measurement Information System (PROMIS) cognitive function short form. A composite score of 0-40 is created with higher scores indicating a better health outcome.
Measured: From baseline to day 120
Change in SF-36 scores
Changes will be calculated for treatments A, B, AB, and C. Linear models will be used to determine treatment effects using the two-stage testing procedure. Will conduct as-treated analysis and linear mixed models will also be fit to examine trends. Soring range is 0-100. a higher score defines a more favorable outcome.
Measured: From baseline to day 120
Local and distant recurrence free survival
Measured: Up to 3 years
Breast cancer specific survival
Measured: Up to 3 years
Overall survival
Measured: Up to 3 years
Incidence of adverse events
Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
Measured: Up to day 120
Adherence rate
Treatment adherence will be evaluated in clinic on day 1 of each cycle and via telephone follow-up on day 2, day 3 of each cycle. Adherence information obtained will include the start and finish time for ingesting the drug and the number of pills ingested. Adherence will also be collected in a pill diary.
Measured: Up to day 120
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2023
- Study start23 Jul 2024
- Primary completion31 Oct 2028 (estimated)
- Study completion31 Oct 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Anatomic Stage I Breast Cancer American Joint Committee on Cancer (AJCC) v8Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 164 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI), Rising Tide Foundation
- Responsible party
- Sponsor
- Investigators
- Mina S Sedrak, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06113016
- Sponsor's protocol ID
- 23-001171
- Other IDs
- P30CA016042, R01CA280088, NCI-2023-06774
- Acronym
- PROFFi
- Status last verified
- Jul 2026
- First submitted
- 26 Oct 2023
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No