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

• ClinicalTrials.gov Identifier: NCT01857817
• Recruitment Status: Terminated
• First Posted: May 20, 2013
• Last Update Posted: April 26, 2018
• Sponsor: Vicus Therapeutics
• Information provided by (Responsible Party): Vicus Therapeutics

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostatic Neoplasms	Drug: VT-122; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 35 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo Controlled, Multicenter Phase 2 Study of Etodolac and Propranolol in Patients With Clinically Progressive Prostate Cancer
• Study Start Date: June 2013
• Actual Primary Completion Date: April 2016
• Actual Study Completion Date: April 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: VT-122 with physician's choice therapy; 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; The following will be used in the study for VT-122: propranolol 22 mg immediate-release capsules and etodolac 340 mg capsules.; Other Names: propranolol; etodolac
Placebo Comparator: Placebo with physician's choice therapy; 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; The placebo capsules will be prepared to match the active drug.

Outcome Measures

Primary Outcome Measures :

1. Change in prostate specific antigen (PSA) [ Time Frame: baseline (Day 1 Cycle 1) to 12 weeks (Day 1, Cycle 4) ]

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

Inclusion Criteria:

1. Have a confirmed diagnosis of prostate cancer
2. Male participants who are ≥18 years of age
3. In the opinion of the investigator, the participants have a life expectancy of at least 3 months.
4. 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
5. Have a Karnofsky Performance Score (KPS) equal to or greater than 70

6. Have the following laboratory parameters (may be assessed locally):

   1. Platelet count ≥50 x 10E3/µL
   2. Total bilirubin ≤1.5 mg/dL
   3. Serum creatinine ≤1.5 x upper limit of normal (ULN) or creatinine clearance >60 mL/min calculated using Cockcroft-Gault
   4. Liver enzymes [aspartate transaminase (AST), alanine transaminase (ALT)] ≤2 x ULN
7. 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:

1. The patient has a history of another primary cancer, with the exception of:

   1. Curatively resected non-melanomatous skin cancer;
   2. 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.
2. Contraindication to propranolol, etodolac
3. Patients on beta blockers
4. Patients receiving chemotherapy (e.g., docetaxel, cabazitaxel, taxane, or platinum as single agents or in combination) as their cancer treatment
5. 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
6. Hypotension at the time of screening (i.e., systolic blood pressure less than 110 mmHg. Diastolic blood pressure less than 60 mmHg)
7. Resting heart rate less than 60 bpm at time of screening
8. 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.
9. On chronotropic drugs (acetylcholine, digoxin, diltiazem, verapamil, atropine, dopamine, dobutamine, epinephrine, isoproterenol)
10. Active clinically serious infections [> Grade 2 National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0]
11. 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
12. 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)
13. 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
14. Patients with uncontrolled diabetes or insulin resistance
15. Participation in any other investigational trial in which receipt of investigational drug or device occurred within 30 days prior to screening for this study

Contacts and Locations

Locations

United States, Arkansas

Highlands Oncology Group

Fayetteville, Arkansas, United States, 72703

United States, California

Redwood Regional Medical Group

Santa Rosa, California, United States, 95403

United States, Colorado

Advanced Urology

Parker, Colorado, United States, 80134

United States, Florida

Manatee Medical Research Institute, LLC

Bradenton, Florida, United States, 34205

Baptist Cancer Institute

Jacksonville, Florida, United States, 32207

United States, Illinois

Midwestern Regional Medical Center

Zion, Illinois, United States, 60099

United States, Michigan

Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Detroit Clinical Research Center, PC

Lansing, Michigan, United States, 48912

United States, Minnesota

Adult & Pediatric Urology

Sartell, Minnesota, United States, 56377

United States, New York

Montefiore Medical Center

Bronx, New York, United States, 10467

AccuMed Research Associates

Garden City, New York, United States, 11530

Premier Medical Group of the Hudson Valley PC

Poughkeepsie, New York, United States, 12601

United States, Texas

Hendrick Cancer Center

Abilene, Texas, United States, 79601

Oncology Consultants, P.A.

Houston, Texas, United States, 77030

United States, Washington

Virginia Mason Medical Center

Seattle, Washington, United States, 98101

Medical Oncology Associates, PS

Spokane, Washington, United States, 99208

Sponsors and Collaborators

Vicus Therapeutics

More Information

• Responsible Party: Vicus Therapeutics
• ClinicalTrials.gov Identifier: NCT01857817
• Other Study ID Numbers: VT1-SYS-601
• First Posted: May 20, 2013
• Last Update Posted: April 26, 2018
• Last Verified: April 2018

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Etodolac; Propranolol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors