This phase II trial test whether dasatinib and quercetin or fisetin alone work in reducing senescence and improving frailty in adult survivors of childhood cancer. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Quercetin and fisetin, are both flavonoids, naturally occurring compounds present in many fruits and vegetables. Quercetin and fisetin has antioxidant and anti-inflammatory effects that might help reduce swelling and kill cancer cells. Giving dasatinib and quercetin or fisetin may kill more cancer cells in adult survivors of childhood cancer.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT04733534.
PRIMARY OBJECTIVE:
I. To test the efficacy of two, short duration senolytic regimens: 1) combination of dasatinib plus quercetin and 2) fisetin alone, to improve walking speed and decrease senescent cell abundance in blood (p16INKA).
SECONDARY OBJECTIVE:
I. To test the safety and tolerability of two different senolytic therapies.
EXPLORATORY OBJECTIVES:
I. To compare the efficacy of the two senolytic regimens in improving walking speed and decreasing senescent cell abundance.
II. To evaluate the longitudinal pattern in measures of frailty.
OUTLINE: Patients will be randomized in 1 of 2 arms.
ARM I: Patients receive dasatinib orally (PO) once daily (QD) and quercetin PO twice daily (BID) on days 1, 2, 3, 30, 31, and 32 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and dual X-ray absorptiometry (DEXA) scan on study.
ARM II: Patients receive fisetin PO on days 1, 2, 30, and 31 in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and DEXA scan on study.
After completion of study treatment, patients are followed up at 30 and 90 days.
Lead OrganizationSaint Jude Children's Research Hospital
Principal InvestigatorGregory Thomas Armstrong
