Treatment of Frailty With Fisetin (TROFFi) in Breast Cancer Survivors

Study Overview
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Brief Summary
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This phase II trial tests whether fisetin works to improve physical function in older women who have received chemotherapy for stage I-III breast cancer treatment. Fisetin is a naturally occurring substance that is found in strawberries and other foods. Fisetin eliminates 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 causes inflammation and damages nearby healthy cells. Studies have shown that chemotherapy causes a build-up of these senescent cells. Giving fisetin may eliminate senescent cells and improve physical function in postmenopausal women who have received chemotherapy for breast cancer.

Detailed Description
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PRIMARY OBJECTIVE: I. To determine the effect of fisetin on physical function, as assessed using the 6-minute walk distance (6MWD), in postmenopausal breast cancer survivors. SECONDARY OBJECTIVES: I. To determine the effect of fisetin on other measures of physical function (grip strength, short physical performance battery [SPPB].

Official Title
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A Phase II Randomized Double-Blind Placebo-Controlled Study of Fisetin to Improve Physical Function in Frail Older Breast Cancer Survivors

Conditions
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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

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Drug: Fisetin
* Drug: Placebo Administration
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented informed consent of the participant and/or legally authorized representative Age: >= 65 years at the time of cancer diagnosis Female Baseline diminished 6-minute walk distance (< 400m). Must be able to ambulate without assistance from another individual. Supportive devices such as a cane or walker are allowed History of resected stage I-III breast cancer treated with neo/adjuvant chemotherapy Must have completed chemotherapy within 12 months. Must have been postmenopausal at the time of cancer diagnosis Exclusion Criteria: Surgery and/or radiation within the last 30 days (Exception: invasive non- major procedures such as an outpatient biopsy) On herbal and natural medications (Exception: cannabidiol (CBD), vitamin C, and vitamin D) and unable or unwilling to hold its administration 2 days prior to and during study treatment dosing Issues with tolerating oral medication (such as but not limited to, inability to swallow pills (g-tubes not allowed), malabsorption issues, ongoing nausea or vomiting during screening, history of Crohn's, gastric bypass/reduction, or celiac disease)

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A (fisetin)<br>Patients receive fisetin PO on the trial. Patients also undergo collection of blood throughout the trial. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Fisetin<br>* Given PO<br>* Other names: 7,3',4'-Flavon-3-ol;Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|
| Placebo Comparator: Arm B (placebo)<br>Patients receive placebo PO on the trial. Patients also undergo collection of blood throughout the trial. | Procedure: Biospecimen Collection<br>* Undergo collection of blood<br>* Other names: Specimen Collection;Drug: Placebo Administration<br>* Given PO<br>Other: Quality-of-Life Assessment<br>* Ancillary studies<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 6-minute walk distance (6MWD) | The 6MWD is a validated measure of physical function. Participants walk at their own pace for 6 minutes and distance (in meters) is measured at the end. Will be treated as a continuous variable. Its distribution will be transformed to normality as appropriate, Initially, a simple t-test will be used to compare the means of 6MWD at Day 60 by treatment groups. | Baseline to day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in grip strength | Generalized estimating equation (GEE) models will be fitted. The variables also will be dichotomized (e.g., < median, >= median) and GEE models for binary data used to test treatment effects over time. | From baseline to day 60 | 
| Change in short physical performance battery (SPPB) score | GEE models will be fitted. The variables also will be dichotomized (e.g., < median, >= median) and GEE models for binary data used to test treatment effects over time. | From baseline to day 60 |