Testing the Synergism of Phytonutrients, Curcumin and Ursolic Acid, to Target Molecular Pathways in the Prostate

Testing the Synergism of Phytonutrients, Curcumin and Ursolic Acid, to Target Molecular Pathways in the Prostate

Phase I Clinical Trial Testing the Synergism of Phytonutrients, Curcumin and Ursolic Acid, to Target Molecular Pathways in the Prostate

No subjects were enrolled in this study, the PI will seek funding and revise the protocol for resubmisson at a later date

A proof of concept clinical trial to assess the synergism of curcumin (CURC) and ursolic acid (UA). Before further testing within formal cancer clinical trials, we must (1) evaluate the bioavailability and safety, (2) confirm the presence of metabolites in the target organ, and (3) validate the appropriate mechanism of effect

Once a subject is identified that may meet eligibility criteria, the physician and/or study investigators will be alerted to the potential candidate and will introduce the study to the patient at their standard of care (SOC) appointment or via telephone. Patients will be given the option for enrollment and if they agree, informed consent will be discussed and obtained provided they meet all inclusion/exclusion criteria. Following informed consent, subjects will be assigned to one of the following cohorts: Cohort 1: • Ursolic Acid (150 mg) BID (twice a day) Cohort 2: • Curcumin (600 mg) BID Cohort 3: • Ursolic Acid (150 mg) and Curcumin (600 mg) BID The study team aim to enroll 10 subjects who will complete the study into each cohort for a total of 30 completers. Subjects will be enrolled on a rolling basis with the first ten subjects assigned to Cohort 1, the next ten subjects assigned to Cohort 2, and the last 10 subjects assigned to Cohort 3.

Administration of Ursolic Acid and Curcumin to subjects who are scheduled to undergo radical prostatectomy

Safety will be compared to evaluate the number, frequency, duration, and relation of toxicity events to CURC/UA combination, as defined by the Common Terminology Criteria for Adverse Events (CTCAE) v 4.03.

Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed.

The pharmacokinetic parameter, the area under the curve (Tmax) representing the time it takes to reach Cmax of ursolic acid, curcumin, and their metabolites will be graphed.

The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed.

Immunohistochemistry of proportion of nuclear p65 NFkB staining before and after prostatectomy on FFPE samples will be completed.

Inclusion Criteria: Have proven diagnosis of prostate cancer with Gleason Group 3 or lower and planning to undergo radical prostatectomy Be able to give informed consent Be age 18 or older Able to stop supplements Exclusion Criteria: Unable to give informed consent Age < 18 High-risk prostate cancer or suspected metastasis Unable to swallow pills Unable to stop supplements

De-identified individual participant data will be available upon completion of the study for approx. 1 year.