A Phase II Randomized Placebo-Controlled Study of Fisetin and Exercise to Prevent Frailty in Breast Cancer Survivors
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 164
- 试验地点
- 12
- 主要终点
- Change in 6 minute walk distance (6MWD)
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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. GFR (mL/min/1.73 m²) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African American)
- •Ability to understand and the willingness to sign a written informed consent document
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Fisetin (Drug)
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.
干预措施: Fisetin (Drug)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Placebo Administration (Drug)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Educational Intervention (Other)
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.
干预措施: Physical Performance Testing (Other)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Exercise Intervention (Other)
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.
干预措施: Physical Performance Testing (Other)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Exercise Intervention (Other)
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.
干预措施: Physical Performance Testing (Other)
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.
干预措施: Quality-of-Life Assessment (Other)
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.
干预措施: Questionnaire Administration (Other)
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.
干预措施: Biospecimen Collection (Procedure)
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.
干预措施: Educational Intervention (Other)
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.
干预措施: Physical Performance Testing (Other)
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.
干预措施: Placebo Administration (Drug)
结局指标
主要结局
Change in 6 minute walk distance (6MWD)
时间窗: 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).
次要结局
- Change in step count(From baseline to day 120)
- Change in frailty phenotype(From baseline to day 120)
- Change in heart rate(From baseline to day 120)
- Change in short physical performance battery (SPPB)(From baseline to day 120)
- Change in physical function subsection of Short Form (SF)-36(From baseline to day 120)
- Change in Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) scores(From baseline to day 120)
- Change in grip strength(From baseline to day 120)
- Change in the Borg Rating of Perceived Exertion (RPE)(From baseline to day 120)
- Change in Patient Reported Outcomes Measurement Information System (PROMIS) cognitive function short form score(From baseline to day 120)
- Breast cancer specific survival(Up to 3 years)
- Change in SF-36 scores(From baseline to day 120)
- Local and distant recurrence free survival(Up to 3 years)
- Overall survival(Up to 3 years)
- Incidence of adverse events(Up to day 120)
- Adherence rate(Up to day 120)