Efficacy and Safety Study of Etodolac and Propranolol in Patients With Clinically Progressive Prostate Cancer

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate the clinical benefit of the co-administration of propranolol and etodolac (VT-122 therapy) in patients with clinically progressive prostate cancer.

Official Title
-----------------
A Randomized, Placebo Controlled, Multicenter Phase 2 Study of Etodolac and Propranolol in Patients With Clinically Progressive Prostate Cancer

Conditions
-----------------
Prostatic Neoplasms

Intervention / Treatment
-----------------
* Drug: VT-122
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a confirmed diagnosis of prostate cancer Male participants who are ≥18 years of age In the opinion of the investigator, the participants have a life expectancy of at least 3 months. Two consecutively rising PSA values or two out of three rising PSA values (2.0 ng/mL is the minimum ending value for PSA) at a minimum of 1-week intervals Have a Karnofsky Performance Score (KPS) equal to or greater than 70 Have the following laboratory parameters (may be assessed locally): Platelet count ≥50 x 10E3/µL Total bilirubin ≤1.5 mg/dL Serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance >60 mL/min calculated using Cockcroft-Gault Liver enzymes [aspartate transaminase (AST), alanine transaminase (ALT)] ≤2 x ULN Able to provide written informed consent prior to any study specific screening procedures with the understanding that the patient has the right to withdraw from the study at any time, for any reason without prejudice Exclusion Criteria: The patient has a history of another primary cancer, with the exception of: Curatively resected non-melanomatous skin cancer; Other primary solid tumor with no known active disease presents that in the opinion of the investigator that will not affect patient outcome in the setting of current prostate cancer diagnosis. Contraindication to propranolol, etodolac Patients on beta blockers Patients receiving chemotherapy (e.g., docetaxel, cabazitaxel, taxane, or platinum as single agents or in combination) as their cancer treatment History or evidence of cardiac disease: congestive heart failure; New York Heart Association class 2 or greater; active coronary artery disease; unstable angina, cardiac arrhythmias requiring anti-arrhythmic therapy, atrio-ventricular block of second or third degree, or uncontrolled hypertension, patients with recent (less than 6 months) myocardial infarction (MI) or coronary revascularization Hypotension at the time of screening (i.e., systolic blood pressure less than 110 mmHg. Diastolic blood pressure less than 60 mmHg) Resting heart rate less than 60 bpm at time of screening Any uncontrolled, intercurrent illness that in the opinion of the Investigator may interfere with study evaluation. Participants with uncontrolled diabetes will be excluded from the study. On chronotropic drugs (acetylcholine, digoxin, diltiazem, verapamil, atropine, dopamine, dobutamine, epinephrine, isoproterenol) Active clinically serious infections [> Grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0] Substance abuse, medical, psychological or social conditions that may, in the opinion of the investigator, interfere with the patient's participation in the study or evaluation of the study results Known or suspected allergy to the investigational agents or any agent given in association with this trial (hypersensitivity reaction, hives, rash, difficulty breathing swelling of your face, lips, tongue, or throat) Any condition that is unstable or which in the opinion of the Investigator could jeopardize the safety of the patient and his/her compliance in the study Patients with uncontrolled diabetes or insulin resistance Participation in any other investigational trial in which receipt of investigational drug or device occurred within 30 days prior to screening for this study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VT-122 with physician's choice therapy<br>Participants will receive oral doses of 66 mg propranolol and 680 mg etodolac daily. Propranolol will be administered 44 mg with breakfast and 22 mg in the mid-afternoon (3PM). Etodolac will be administered 340 mg with breakfast and 340 mg with dinner. | Drug: VT-122<br>* The following will be used in the study for VT-122: propranolol 22 mg immediate-release capsules and etodolac 340 mg capsules.<br>* Other names: etodolac;|
| Placebo Comparator: Placebo with physician's choice therapy<br>Participants will receive physician's choice therapy as the standard of care as well as the placebo capsules that are of the same weight as propranolol and etodolac. | Drug: Placebo<br>* The placebo capsules will be prepared to match the active drug.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in prostate specific antigen (PSA) |  | baseline (Day 1 Cycle 1) to 12 weeks (Day 1, Cycle 4) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PSA progression |  | baseline to 12 weeks | 
| PSA doubling time (PSADT) |  | baseline and every month during treatment | 
| Change in self-reported performance (EQ-5D), pain (visual analog scale [VAS] and opiate usage) |  | Day 1 Cycle 1, on Day 1 of each subsequent 28-day cycle, and on end of treatment | 
| Time to symptom progression (TTSP) |  | Day 1 Cycle 1 and Day 1 of each subsequent 28-day cycle | 
| Change in correlative biomarkers |  | Day 1 Cycle 1, on Day 1 of each subsequent 28-day cycle, and on end of treatment |