Pilot Study of Fisetin to Improve Fatigue Among Older Adult Cancer Survivors

Overview

The purpose of this study is to find out if taking a Fisetin supplement can decrease fatigue among older cancer survivors.

Detailed description

Prospective double-blind placebo controlled, 14-day cross-over trial of patients aged 65 and over with a history of cancer with self-reported fatigue. Participants will be randomized and provided with Fisetin pills or placebo to take twice daily on two consecutive days for two consecutive weeks. Participants will return on day 14 for a blood draw followed by a 14 day wash-out. At the four-week visit participants will receive a cross-over placebo-controlled dosing regimen over two weeks. Follow-up phone calls for safety assessment and adherence review will occur at weeks 1 and 5. Follow-up assessments will be completed at 2, 4 and 6 weeks, and a post-treatment phone call assessment completed at 12 weeks.

Interventions

• Drug Fisetin followed by Placebo
  Fisetin 20 mg/kg per dose twice daily on two consecutive days for two consecutive weeks. Participants will return on day 14 for a blood draw followed by a 14-day wash-out. At the 4-week visit participants will receive a cross-over placebo-controlled dosing regimen to be taken twice daily on two consecutive days for two consecutive weeks.
• Drug Placebo followed by Fisetin
  Placebo twice daily on two consecutive days for two consecutive weeks. Participants will return on day 14 for a blood draw followed by a 14-day wash-out. At the 4-week visit participants will receive a cross-over Fisetin 20 mg/kg per dose twice daily on two consecutive days for two consecutive weeks.

Primary outcome measures

• Change in Pittsburgh Fatigability Scale (PFS) [Time frame: Baseline to Week 2]
• Change in Pittsburgh Fatigability Scale (PFS) [Time frame: Baseline to Week 4]
• Change in Pittsburgh Fatigability Scale (PFS) [Time frame: Baseline to Week 6]
• Change in Pittsburgh Fatigability Scale (PFS) [Time frame: Baseline to Week 12]

Secondary outcome measures (8)

• Change in Patient Reported Outcomes Measurement System (PROMIS) [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6, Baseline to Week 12]
• Change in Pepper Assessment Tool for Disability (PAT-D) [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6]
• Change in Expanded Short Physical Performance Battery (eSPPB) [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6]
• Change in 6-minute Walk Distance [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6]
• Change in Fried Frailty Phenotype Score [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6]
• Change in Longitudinal Aging Study Amsterdam (LASA) Sedentary Behavior Questionnaire [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6]
• Change in PROMIS Global Health Short Form [Time frame: Baseline to Week 2, Baseline to Week 4, Baseline to Week 6]
• Medication Adherence Rate [Time frame: Week 2, Week 5]

Eligibility criteria

Inclusion criteria

• Self-reported history of cancer diagnosed > 12 months prior to enrollment excluding non-melanoma skin cancer with no evidence of disease at enrollment.
• Eligible solid tumor cancer types include Stage 1-3 breast, lung, head and neck, colorectal, anal, prostate, melanoma, bladder/ureteral, esophageal, gastric, pancreatic, kidney, liver/biliary, uterine, cervical, ovarian, sarcoma. (superficial disease and in situ disease only is excluded)
• Eligible hematologic malignancies include lymphoma any subtype any stage in remission, multiple myeloma in remission, leukemia any subtype in remission.
• Eligible prior cancer treatment modalities include surgery, radiation, chemotherapy, hormonal therapies, immunotherapy, biologic therapies.
• All anti-cancer therapy completed > 6 months prior to enrollment with < 5 years from treatment
• Presence of self-reported fatigue defined by a response of "somewhat, quite a bit, or very much" to the screening question "During the past seven days, did you feel fatigued: Not at all, a little bit, somewhat, quite a bit, very much?"
• Ability to walk without requiring assistance from another individual (use of cane or walker acceptable)
• Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).

Exclusion criteria

• Unable or unwilling to give informed consent
• Female patients are of childbearing potential, defined as postmenopausal for at least 1 year.
• Prisoners, institutionalized individuals, or others who may be considered vulnerable populations, such as individuals with dementia
• Currently taking warfarin or Coumadin
• Currently taking a steroid medication either regularly or within the last two weeks.
• Patients currently taking medications that are sensitive to substrates or substrates with a narrow therapeutic range for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, OATP1B1 (Unless willing and able to stop or modify the dosing of the drug) or strong inhibitors or inducers of CYP3A4 (e.g., cyclosporine, tacrolimus, or sirolimus) are excluded, unless medication can be safely held during the following times:
• Immediately before the 1st IP administration (Day 0 or Day 30) until at least 10 hours after the 2nd IP administration (Day 1 or Day 31)
• Immediately before the 3rd IP administration (Day 7 or Day 37) until at least 10 hours after the 4th IP administration (Day 8 or Day 38)
• Subjects taking any of the medications listed in Appendix I may participate if they are otherwise eligible AND the medication can be safely held during the following times: Immediately before the 1st IP administration (Day 0 or Day 30) until at least 10 hours after the 2nd IP administration (Day 1 or Day 31); Immediately before the 3rd IP administration (Day 7 or Day 37) until at least 10 hours after the 4th IP administration (Day 8 or Day 38)
• Drugs listed as part of the exclusion criteria are not permitted during each of the two 2-day courses of treatment with Fisetin. If patients are required to initiate these medications within the 2-day period, they will be removed from the study primarily due to risk of drug-drug interaction.
• Uncontrolled hypertension (systolic >170 OR diastolic >100 mmHg) upon repeated assessments
• Uncontrolled (as per clinical judgement) pleural/pericardial effusions or ascites
• Active malignancy or on-going cancer treatment including oral anti-estrogen therapy, immunotherapy, biologic therapy.
• Men receiving androgen deprivation therapy
• Symptomatic congestive heart failure
• Lung disease requiring oxygen
• End stage renal disease requiring dialysis
• Inability to swallow capsules
• Chronic nausea or diarrhea defined by a frequency of ≥ once per week
• Diagnosis of dementia
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known untreated hypothyroidism
• Allergy to fisetin
• Human immunodeficiency virus infection
• Known active untreated hepatitis B or C infection
• Active invasive fungal infection
• Unwilling to provide informed consent, including consent to access electronic health records
• Judged unsuitable for the trial for any reason by research team
• The following laboratory tests as indicated or as per clinical judgement: Normal organ and marrow function as defined: Hemoglobin <10g/dL, leukocytes <3,000/mcL, absolute neutrophil count <1,500/mcL, platelets <100,000/mcL, total bilirubin above normal institutional limits, AST(SGOT)/ALT(SGPT) >2.5 X institutional upper limit of normal, creatinine clearance <30 mL/min, fasting glucose >300 on day of screening (from plasma or serum)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Quadruple blind

Primary purpose

Other

Study locations

United States · 1 center

• Atrium Health Wake Forest Baptist Hospital — Winston-Salem

Identifiers

NCT: NCT06819254 · IRB00125637

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗