- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06113016
Prevention of Frailty With Fisetin and Exercise (PROFFi) in Breast Cancer Survivors (PROFFi)
A Phase II Randomized Placebo-Controlled Study of Fisetin and Exercise to Prevent Frailty in Breast Cancer Survivors
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90095
- UCLA / Jonsson Comprehensive Cancer Center
-
Contact:
- Mina S. Sedrak
- Phone Number: 310-825-3181
- Email: msedrak@mednet.ucla.edu
-
Principal Investigator:
- Mina S. Sedrak
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Arm A (fisetin, physical activity handout)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Undergo collection of blood samples
Other Names:
Given PO
Other Names:
Ancillary studies
Other Names:
Receive handout on physical activity
Other Names:
|
Experimental: Arm AB (fisetin, tailored exercise training)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Undergo collection of blood samples
Other Names:
Given PO
Other Names:
Ancillary studies
Other Names:
Receive individually tailored exercise intervention
|
Active Comparator: Arm B (placebo, tailored exercise training)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Undergo collection of blood samples
Other Names:
Given PO
Ancillary studies
Other Names:
Receive individually tailored exercise intervention
|
Active Comparator: Arm C (placebo, physical activity handout)
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.
|
Ancillary studies
Other Names:
Ancillary studies
Undergo collection of blood samples
Other Names:
Given PO
Ancillary studies
Other Names:
Receive handout on physical activity
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in 6 minute walk distance (6MWD)
Time Frame: From baseline to day 120
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: Up to 3 years
|
Up to 3 years
|
|
Change in heart rate
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in step count
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in short physical performance battery (SPPB)
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in grip strength
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in frailty phenotype
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in physical function subsection of Short Form (SF)-36
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in the Borg Rating of Perceived Exertion (RPE)
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Local and distant recurrence free survival
Time Frame: Up to 3 years
|
Up to 3 years
|
|
Breast cancer specific survival
Time Frame: Up to 3 years
|
Up to 3 years
|
|
Incidence of adverse events
Time Frame: Up to day 120
|
Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
|
Up to day 120
|
Adherence rate
Time Frame: Up to day 120
|
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.
|
Up to day 120
|
Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) scores
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in Patient Reported Outcomes Measurement Information System (PROMIS) cognitive function short form score
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Change in SF-36 scores
Time Frame: From baseline to day 120
|
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.
|
From baseline to day 120
|
Collaborators and Investigators
Investigators
- Principal Investigator: Mina S Sedrak, UCLA / Jonsson Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 23-001171
- P30CA016042 (U.S. NIH Grant/Contract)
- NCI-2023-06774 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- R01CA280088 (U.S. NIH Grant/Contract)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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