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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Ursolic Acid
* Drug: Curcumin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects will be assigned to one of 3 cohorts, starting with cohort 1 and progressing to cohort 3
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ursolic Acid<br>Administration of Ursolic Acid to subjects who are scheduled to undergo radical prostatectomy | Drug: Ursolic Acid<br>* Ursolic Acid 150mg<br>|
| Experimental: Curcumin<br>Administration of Curcumin to subjects who are scheduled to undergo radical prostatectomy | Drug: Curcumin<br>* Curcumin 600mg<br>|
| Experimental: Ursolic Acid and Curcumin<br>Administration of Ursolic Acid and Curcumin to subjects who are scheduled to undergo radical prostatectomy | Drug: Ursolic Acid<br>* Ursolic Acid 150mg<br>Drug: Curcumin<br>* Curcumin 600mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number, frequency, duration, and relation of toxicity events | 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. | Baseline to 8 weeks | 
| Peak serum concentration | Dose response curve representing the pharmacokinetic parameter peak serum concentration (Cmax) of ursolic acid, curcumin, and their metabolites will be graphed. | Baseline to 8 weeks | 
| Time to reach peak serum concentration | 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. | Baseline to 8 weeks | 
| Half-life | The pharmacokinetic parameter, half-life of ursolic acid, curcumin, and their metabolites will be graphed. | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Levels of UA, CURC, and metabolites in prostate tissue | Identify the presence and levels of UA, CURC and their metabolites in prostate tissue using HPLC. | Baseline to 8 weeks | 
| Immunohistochemistry measurement | Immunohistochemistry of proportion of nuclear p65 NFkB staining before and after prostatectomy on FFPE samples will be completed. | Baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radical Prostatectomy