A Randomized, Placebo Controlled, Multicenter Phase 2 Study of Etodolac and Propranolol in Patients With Clinically Progressive Prostate Cancer
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. Able to take food or nutritional support.
5. Two consecutively rising PSA values at a minimum of 1-week intervals (2.0 ng/mL is
the minimum starting value for PSA) OR appearance of one or more new or progressing
lesions on bone scans
6. Have a KPS equal to or greater than 70.
7. Have the following laboratory parameters (may be assessed locally):
1. Platelet count ≥50 x 10E9/L.
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
8. 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.
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. However, patients on beta blockers for the treatment of
hypertension are allowed if they change to a different drug class, e.g., some classes
of angiotensin-converting enzyme (ACE) inhibitors, for controlling hypertension at
least two weeks before randomization.
4. Patients receiving biologic therapy 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. Symptomatic and uncontrolled brain symptoms due to tumors or metastases requiring
systemic steroid administration of >5 mg/day
12. 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.
13. 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).
14. Inability to take oral medications
15. 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.
16. Patients with uncontrolled diabetes or insulin resistance.
17. Participation in any other investigational trial in which receipt of investigational
drug or device occurred within 30 days prior to screening for this study.