Fatty Acid Synthase Inhibition in Castration Refractory Prostate Cancer (FASN)

FASN Fatty Acid Synthase Inhibition in Castration Refractory Prostate Cancer Salvaging Taxane Failure

The purpose of this research study is to find out what effects (good and bad) omeprazole and cabazitaxel, or omeprazole and docetaxel, has on participants and their condition. Investigators believe omeprazole may help the other medications work.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer; Refractory Cancer; Castration Resistant Prostatic Cancer
• Intervention / Treatment: Drug: Omeprazole 80 mg twice daily

Detailed Description

Primary Objective(s): Obtain Overall Response Rate (ORR) to taxane therapy by adding the fatty acid synthase inhibitor, omeprazole to the current "failing" taxane regimen in 15% of subjects using Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria, defined by partial response (PR) or complete response (CR)

Secondary Objectives (only at patients treated at Wake Forest Baptist Comprehensive Cancer Center main campus):

• Pharmacodynamics-demonstrate omeprazole in vivo fatty acid synthase inhibition by 11C-Acetate PET/CT (3-6) Non-invasive approach to demonstrate the fatty acid synthase inhibitor (omeprazole) is hitting its target
• Obtain a prostate specific antigen response rate by adding the fatty acid synthase inhibitor omeprazole to the current "failing" taxane regimen. (16)
• Measure pain using the Patient-Reported Outcomes Measurement Information System (PROMIS) at Baseline, Cycle 5, Cycle 12, and every cycle thereafter.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Nurse; Phone Number: 336-716-5440; Email: jethomas@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Salisbury, North Carolina, United States, 28144
      • Recruiting
      • W.G. Bill Hefner VA Medical Center
      • Principal Investigator: Michael Goodman, MD
      • Contact: Study Coordinator; Email: ahumbert@wakehealth.edu
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Comprehensive Cancer Center
      • Principal Investigator: Michael Goodman, MD
      • Contact: Study Coordinator; Email: ahumbert@wakehealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have castrate refractory prostate cancer with prior taxane treatment (docetaxel or cabazitaxel) which was used in the castrate refractory setting
• Cancer Progression as defined by PCWG3
• Age 18 or older.
• ECOG 0, 1, or 2
• Life expectancy of greater than 2 months
• Men must agree to use adequate contraception (barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
• Ability to understand and the willingness to sign an IRB-approved informed consent document (either directly or via a legally authorized representative).
• Organ & marrow function as defined below: Absolute neutrophil count >1,200/mcL Platelets >75,000/mcL; total bilirubin= within normal institutional limits; AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal; creatinine <2.5 X institutional upper limit of normal

Exclusion Criteria:

• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to omeprazole or taxane therapy.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Omeprazole Plus Standard of Care for Prostate Cancer Regimen; This intervention will be given on an outpatient basis. Omeprazole, 80 mg twice daily.

Drug: Omeprazole 80 mg twice daily; Participants will be treated with omeprazole 80 mg twice daily on Day 0. Within 10 days of starting omeprazole, participants will be treated with standard prostate cancer dosing of every three week docetaxel or cabazitaxel based on package insert. Participants that have only had docetaxel will be retreated with docetaxel along with concurrent omeprazole. Patients that have had both docetaxel and cabazitaxel will be retreated with either cabazitaxel or docetaxel (investigators choice) along with concurrent omeprazole. However investigators encourage investigator to choose cabazitaxel in patients previously treated with cabazitaxel.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change Radiographic Response - RECIST 1.1	Response will be defined by RECIST 1.1 as defined by Prostate Cancer Clinical Trials Working Group 3 definition for complete response (CR) - disappearance of all target lesions); partial response (PR) (at least a 30% decrease in the sum of diameters of target lesions); progressive disease (PD) (at least a 20% increase in the sum of diameters or target lesions); stable disease (SD) (neither sufficient shrinkage to qualify for partial response nor sufficient to qualify for progressive disease); or not evaluable (NE).	At 3, 6 and 9 months
Change in Bone Metastasis Response - Prostate Cancer Clinical Trials Working Group 3 (PCWG3)	Response will be defined by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) for complete response (CR), partial response (PR), progressive disease (PD), stable disease (SD) or not evaluable (NE).	At 3, 6 and 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatty Acid Synthase Activity - Pre Omeprazole Use	Performed only on the first 10 participants by utilizing the 11C acetate tracer in the PET scan to evaluate the fatty acid synthase activity prior to omeprazole by examining changes in the values of standardized uptake. we will perform a two-sample t-test to see whether the change in SUV values is different between patients with an objective response versus those without an objective response.	At baseline
Fatty Acid Synthase Activity - Post Omeprazole Use	Evaluating the first 10 participants by utilizing the 11C acetate tracer in the PET scan to evaluate the fatty acid synthase activity prior to omeprazole by examining changes in the values of standardized uptake. we will perform a two-sample t-test to see whether the change in SUV values is different between patients with an objective response versus those without an objective response.	Up to approximately 2 years
Prostate Specific Antigen (PSA) Progression	Investigators will collect PSA to determine whether PSA progression is positive or negative. Positive meaning that PSA slope is getting worse over time than it was prior to treatment and negative meaning PSA slope is improving after treatment when compared to baseline.	At baseline and up to approximately 2 years
Prostate Specific Antigen (PSA) Response	Investigators will examine a PSA response rate (baseline on clinical definition of PSA response). In this analysis investigators will determine for each participant if they are a PSA responder (yes/no) and then using this data will estimate a 95% exact Clopper Pearson binomial interval for the PSA response rate.	At baseline and up to approximately 2 years
Patient Reported Outcome - Pain	Participants will report pain intensity at Cycle 1 Day 1 (baseline) compared to Cycle 5, Day 1 and Day 1 of every subsequent cycle on numeric scale of 0-to-10 (0 = no pain, 10 = worse imaginable pain). A paired t-test will be performed to determine whether the Pain score improved or worsened in patients after treatment.	At baseline, 12 weeks, and Day 1 of every subsequent cycle (each cycle is 28 days) up to approximately 2 years

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Michael Goodman, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 2, 2020
• First Submitted That Met QC Criteria: April 3, 2020
• First Posted (Actual): April 7, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Omeprazole
• Other Study ID Numbers: IRB00068039; P30CA012197 (U.S. NIH Grant/Contract); WFBCC 85220 (Other Identifier: Wake Forest Baptist Comprehensive Cancer Center)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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.: No