Trial Title:
Prevention of Frailty With Fisetin and Exercise (PROFFi) in Breast Cancer Survivors
NCT ID:
NCT06113016
Condition:
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
Conditions: Official terms:
Breast Neoplasms
Frailty
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Supportive Care
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking description:
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.
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo collection of blood samples
Arm group label:
Arm A (fisetin, physical activity handout)
Arm group label:
Arm AB (fisetin, tailored exercise training)
Arm group label:
Arm B (placebo, tailored exercise training)
Arm group label:
Arm C (placebo, physical activity handout)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Other
Intervention name:
Educational Intervention
Description:
Receive handout on physical activity
Arm group label:
Arm A (fisetin, physical activity handout)
Arm group label:
Arm C (placebo, physical activity handout)
Other name:
Education for Intervention
Other name:
Intervention by Education
Other name:
Intervention through Education
Other name:
Intervention, Educational
Intervention type:
Other
Intervention name:
Exercise Intervention
Description:
Receive individually tailored exercise intervention
Arm group label:
Arm AB (fisetin, tailored exercise training)
Arm group label:
Arm B (placebo, tailored exercise training)
Intervention type:
Drug
Intervention name:
Fisetin
Description:
Given PO
Arm group label:
Arm A (fisetin, physical activity handout)
Arm group label:
Arm AB (fisetin, tailored exercise training)
Other name:
3,3',4',7-Tetrahydroxyflavone
Other name:
7,3',4'-Flavon-3-ol
Intervention type:
Other
Intervention name:
Physical Performance Testing
Description:
Ancillary studies
Arm group label:
Arm A (fisetin, physical activity handout)
Arm group label:
Arm AB (fisetin, tailored exercise training)
Arm group label:
Arm B (placebo, tailored exercise training)
Arm group label:
Arm C (placebo, physical activity handout)
Other name:
Physical Fitness Testing
Other name:
Physical Function Testing
Intervention type:
Drug
Intervention name:
Placebo Administration
Description:
Given PO
Arm group label:
Arm B (placebo, tailored exercise training)
Arm group label:
Arm C (placebo, physical activity handout)
Intervention type:
Other
Intervention name:
Quality-of-Life Assessment
Description:
Ancillary studies
Arm group label:
Arm A (fisetin, physical activity handout)
Arm group label:
Arm AB (fisetin, tailored exercise training)
Arm group label:
Arm B (placebo, tailored exercise training)
Arm group label:
Arm C (placebo, physical activity handout)
Other name:
Quality of Life Assessment
Intervention type:
Other
Intervention name:
Questionnaire Administration
Description:
Ancillary studies
Arm group label:
Arm A (fisetin, physical activity handout)
Arm group label:
Arm AB (fisetin, tailored exercise training)
Arm group label:
Arm B (placebo, tailored exercise training)
Arm group label:
Arm C (placebo, physical activity handout)
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.
Detailed 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- 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
- 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, 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
Gender:
Female
Minimum age:
N/A
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
UCLA / Jonsson Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mina S. Sedrak
Phone:
310-825-3181
Email:
msedrak@mednet.ucla.edu
Investigator:
Last name:
Mina S. Sedrak
Email:
Principal Investigator
Start date:
April 17, 2024
Completion date:
August 31, 2031
Lead sponsor:
Agency:
Jonsson Comprehensive Cancer Center
Agency class:
Other
Collaborator:
Agency:
National Institutes of Health (NIH)
Agency class:
NIH
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Jonsson Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06113016
