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

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

Study Overview

• Status: Withdrawn
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: Ursolic Acid; Drug: Curcumin

Detailed Description

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.

• Study Type: Interventional
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • San Antonio, Texas, United States, 78229
      • Mays Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ursolic Acid; Administration of Ursolic Acid to subjects who are scheduled to undergo radical prostatectomy	Drug: Ursolic Acid; Ursolic Acid 150mg
Experimental: Curcumin; Administration of Curcumin to subjects who are scheduled to undergo radical prostatectomy	Drug: Curcumin; Curcumin 600mg
Experimental: Ursolic Acid and Curcumin; Administration of Ursolic Acid and Curcumin to subjects who are scheduled to undergo radical prostatectomy	Drug: Ursolic Acid; Ursolic Acid 150mg; Drug: Curcumin; Curcumin 600mg

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center at San Antonio
• Investigators: Principal Investigator: Michael A Liss, MD, University of Texas Health at San Antonio

Study record dates

Study Major Dates

• Study Start (Anticipated): October 1, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: May 21, 2020
• First Submitted That Met QC Criteria: May 21, 2020
• First Posted (Actual): May 27, 2020

Study Record Updates

• Last Update Posted (Actual): September 16, 2021
• Last Update Submitted That Met QC Criteria: September 8, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Radical Prostatectomy
• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Curcumin; Ursolic acid
• Other Study ID Numbers: HSC20190735H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data will be available upon request.
• IPD Sharing Time Frame: De-identified individual participant data will be available upon completion of the study for approx. 1 year.
• IPD Sharing Access Criteria: Access granted upon request.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes