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O estudo clínico NCT06113016 (PROFFi) para Anatomic Stage I Breast Cancer American Joint Committee on Cancer (AJCC) V8, Estágio Anatômico II Câncer de Mama AJCC v8, Estágio Anatômico III Câncer de Mama AJCC v8, Carcinoma de mama em estágio inicial está recrutando. Consulte a visualização em cartões do Radar de Estudos Clínicos e as ferramentas de descoberta de IA para ver todos os detalhes. Ou pergunte qualquer coisa aqui. | ||
Prevention of Frailty With Fisetin and Exercise in Breast Cancer Survivors (PROFFi)
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.
A Phase II Randomized Placebo-Controlled Study of Fisetin and Exercise to Prevent Frailty in Breast Cancer Survivors
| Grupo de participantes/Braço | Intervenção/Tratamento |
|---|---|
Comparador ativoArm 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. | Coleta de biospecimen Undergo collection of blood samples Intervenção educacional Receive handout on physical activity Fisetin Given PO Teste de desempenho físico Ancillary studies Avaliação da qualidade de vida Ancillary studies Administração de questionário Ancillary studies |
ExperimentalArm 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. | Coleta de biospecimen Undergo collection of blood samples Intervenção de exercício Receive individually tailored exercise intervention Fisetin Given PO Teste de desempenho físico Ancillary studies Avaliação da qualidade de vida Ancillary studies Administração de questionário Ancillary studies |
Comparador ativoArm 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. | Coleta de biospecimen Undergo collection of blood samples Intervenção de exercício Receive individually tailored exercise intervention Teste de desempenho físico Ancillary studies Administração de placebo Given PO Avaliação da qualidade de vida Ancillary studies Administração de questionário Ancillary studies |
Comparador ativoArm 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. | Coleta de biospecimen Undergo collection of blood samples Intervenção educacional Receive handout on physical activity Teste de desempenho físico Ancillary studies Administração de placebo Given PO Avaliação da qualidade de vida Ancillary studies Administração de questionário Ancillary studies |
| Medida de desfecho | Descrição da medida | Prazo |
|---|---|---|
Change in 6 minute walk distance (6MWD) | 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 |
| Medida de desfecho | Descrição da medida | Prazo |
|---|---|---|
Change in heart rate | 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 | 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) | 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 | 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 | 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 | 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) | 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 Quality of Life Questionnaire - Chemotherapy-Induced Peripheral Neuropathy 20 (QLQ-CIPN20) scores | 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 | 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 | 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 |
Local and distant recurrence free survival | Up to 3 years | |
Breast cancer specific survival | Up to 3 years | |
Overall survival | Up to 3 years | |
Incidence of adverse events | Measured by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0. | Up to day 120 |
Adherence rate | 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 |
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
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
Jonsson Comprehensive Cancer Center- ⚕️National Institutes of Health (NIH)
Instituto Nacional do Câncer, EUA3028 estudos clínicos ativos para explorar- 🧬Rising Tide Foundation
California