Fatty Acid Synthase Inhibition in Castration Refractory Prostate Cancer

Phase 2

Recruiting

• Conditions: Castration Resistant Prostatic Cancer; Prostate Cancer; Refractory Cancer
• Interventions: Drug: Omeprazole 80 mg twice daily

• Registration Number: NCT04337580
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

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.

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.

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Study First Submitted: 2020-04-02
• Study First Submitted QC: 2020-04-03
• Study First Posted: 2020-04-07
• Study Start: 2021-03-05
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-26
• Primary Completion: 2024-08
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 20

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

Read More

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.

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Change Radiographic Response - RECIST 1.1	At 3, 6 and 9 months	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).
Change in Bone Metastasis Response - Prostate Cancer Clinical Trials Working Group 3 (PCWG3)	At 3, 6 and 9 months	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).

Secondary Outcome Measures

Name	Time	Method
Prostate Specific Antigen (PSA) Progression	At baseline and up to approximately 2 years	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.
Fatty Acid Synthase Activity - Pre Omeprazole Use	At baseline	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.
Fatty Acid Synthase Activity - Post Omeprazole Use	Up to approximately 2 years	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.
Prostate Specific Antigen (PSA) Response	At baseline and up to approximately 2 years	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.
Patient Reported Outcome - Pain	At baseline, 12 weeks, and Day 1 of every subsequent cycle (each cycle is 28 days) up to approximately 2 years	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.

Trial Locations

Locations (2)

Wake Forest Baptist Comprehensive Cancer Center; 🇺🇸 Winston-Salem, North Carolina, United States

W.G. Bill Hefner VA Medical Center; 🇺🇸 Salisbury, North Carolina, United States