A Pilot Study to Enhance F18 FDG-PET Imaging of Prostate Cancers With the Metabolic Inhibitor Ranolazine

Inclusion Criteria

• Written informed consent has been obtained.
• Adults over 18 years of age.
• Histological or cytologically confirmed prostate adenocarcinoma.
• Arm 1 patients must have treatment-naïve, Gleason ≥ 7 prostate cancer based on transrectal ultrasound (TRUS) biopsy, have localized disease, and have decided to undergo radical prostatectomy (open or robotic) as definitive treatment for their prostate cancer.
• Arm 2 patients must have lymph node, soft tissue, bone, or visceral metastatic disease measuring ≥ 1 cm (lytic component if bone), documented by either CT or MRI imaging within 6 weeks of signing consent. Arm 2 patients may have hormone-sensitive or castrate-resistant disease and may be receiving treatment with hormonal therapies.
• For Arm 1 patients, the time from the TRUS prostate biopsy to the planned first study PET scan must be ≥ 1 month. For patients who have undergone prior prostate mapping biopsy, the time from the mapping biopsy to the planned first study PET scan must be ≥ 2 months.
• For Arm 1 patients, participation in this study, in the opinion of the treating physicians, will not introduce delays in surgery that would adversely affect the patient.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Fasting blood glucose ≤ 120 mg/dL.
• Adequate renal function (Creatinine ≤ 1.5 X ULN)
• Adequate hepatic function (bilirubin 50%.
• Have a history of gastrointestinal disorders (medical disorders or extensive surgery) that may interfere with the absorption of ranolazine.
• Documented hypersensitivity to any component of ranolazine (Ranexa®) pills.
• Need for medications that are:
• strong cytochrome P450, family 3, subfamily A (CYP3A) inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, saquinavir),
• moderate CYP3A inhibitors (e.g. diltiazem, verapamil, erythromycin, fluconazole, grapefruit juice or grapefruit-containing products),
• CYP3A inducers (e.g. rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort),
• CYP3A substrates with a narrow therapeutic range (e.g. cyclosporine, tacrolimus, sirolimus),
• P-gp inhibitors or substrates (e.g. cyclosporine, digoxin),
• polypeptide 6 (CYP2D6) substrates (e.g. tricyclic antidepressants and antipsychotics),or
• simvastatin at doses > 20 mg/day.
• Have corrected QT interval (QTc)> 450 msec (male) or > 470 msec (female) on 12-lead electrocardiogram.
• Poorly controlled diabetes, hemoglobin A1c (Hgb A1C) >9 or random blood glucose >250mg/dL.
• Active or symptomatic viral hepatitis or chronic liver disease.
• Clinically significant heart disease as evidenced by:
• myocardial infarction, or
• arterial thrombotic events in the past 6 months,
• severe or unstable angina, or
• New York Heart Association Class III-IV heart disease or
• cardiac ejection fraction measurement of <50%.
• Active infection requiring antibiotics.
• Major surgery or radiation treatment within 3 months.
• Cytotoxic chemotherapy within 4 weeks.
• Immunotherapy within 6 months.
• Any prior therapy with Radium-223, Samarium, or Strontium.
• Arm 1 patients may not have received any prior luteinizing-hormone-releasing hormone (LHRH) agonists/antagonists, anti-androgens, or chemotherapy for their prostate cancer. 5-alpha reductase inhibitors (finasteride, dutasteride) may be allowed.
• Have any condition that, in the opinion of the investigator, would compromise the well-being of the subject or the study or prevent the subject from meeting or performing study requirements.