Clinical trial NCT04337580: Fatty Acid Synthase Inhibition in Castration Refractory Prostate Cancer
Official title: A Phase II Trial of FASN Inhibition by Omeprazole in Combination With Cabazitaxel in Patients With Docetaxel- and Castration-Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Prostate Cancer
Refractory Cancer
Castration Resistant Prostatic Cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2020-04-07
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change Radiographic Response - RECIST 1.1
timeFrame: At 3, 6 and 9 months
measure: Change in Bone Metastasis Response - Prostate Cancer Clinical Trials Working Group 3 (PCWG3)
timeFrame: At 3, 6 and 9 months
Secondary outcomes:
measure: Fatty Acid Synthase Activity - Pre Omeprazole Use
timeFrame: At baseline
measure: Fatty Acid Synthase Activity - Post Omeprazole Use
timeFrame: Up to approximately 2 years
measure: Prostate Specific Antigen (PSA) Progression
timeFrame: At baseline and up to approximately 2 years
measure: Prostate Specific Antigen (PSA) Response
timeFrame: At baseline and up to approximately 2 years
measure: Patient Reported Outcome - Pain
timeFrame: At baseline, 12 weeks, and Day 1 of every subsequent cycle (each cycle is 28 days) up to approximately 2 years
Other outcomes:
Locations:
city: Salisbury
country: United States
facility: W.G. Bill Hefner VA Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Comprehensive Cancer Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Michael Goodman, MD
role: PRINCIPAL_INVESTIGATOR
References: