Fisetin to Improve Physical Function in Postmenopausal Stage I-III Breast Cancer Survivors

• Status: Not yet recruiting
• Trial end date: 2023-12-31
• Target enrollment: 0
• Participant gender: Female

Summary

This phase II trial tests whether fisetin works to improve physical function in postmenopausal 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Collaborator: National Cancer Institute (NCI)

Criteria

Inclusion Criteria:

• Documented informed consent of the participant and/or legally authorized representative

• Age: >= 50 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 at least 3 months but no more than 6 months

• Must have been postmenopausal at the time of cancer diagnosis

• Platelets > 60,000/mm^3

• White blood cell count > 2,000/mm^3

• Absolute neutrophil count > 500/mm^3

• Hemoglobin >= 7.0 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

Exclusion Criteria:

• Chemotherapy, biological therapy, or immunotherapy within 3 months 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 (Exception: invasive non- major procedures such as an outpatient biopsy)

• Subjects taking medications that cannot be stopped 2 days prior to the start of study that are sensitive to substrates or substrates with a narrow therapeutic range for CYP3A4, CYP2C8, CYP2C9, or CYP2D6 or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus or sirolimus) within 14 days prior to the start of study treatment. If antifungals are absolutely necessary from an infectious disease perspective, then they will be allowed only if the levels are therapeutic. Azole antifungals are not allowed (fluconazole, miconazole, voriconazole, itraconazole, posaconazole, isavuconazole)

• On herbal and natural medications (Exception: cannabidiol (CBD) and unable or unwilling to hold its administration 2 days prior to and during study treatment dosing

• On proton pump inhibitors and unable or unwilling to hold therapy 2 days prior to the start of study treatment and during study treatment dosing

• 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.)

• Subjects taking the following antimicrobial agents within 2 days prior to the start of study: aminoglycosides, macrolides (clarithromycin, erythromycin), antivirals (nelfinavir, indinavir, saquinavir, ritonavir, elbasvir/grazoprevir), rifampin

• 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)

• Untreated endocrine disorder such as hypoparathyroidism, hyperparathyroidism, acromegaly, Cushing's syndrome, hypopituitarism. Treated conditions are allowed

• Active infection requiring antibiotics

• 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

• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)