Safety Study of MRI-guided Transurethral Ultrasound Ablation of Prostate Tissue to Treat Localized Prostate Cancer

This study is to evaluate that the MRI-guided transurethral ultrasound therapy system is safe and feasible to ablate prostate tissue in men with localized prostate cancer.

Profound Medical Inc. has developed a novel technology called the MRI-guided transurethral ultrasound therapy system. The technology is developed for patients with organ confined prostate cancer. The therapeutic endpoint of this technology is thermal coagulation of prostate tissue.

The treatment is conducted completely within an MRI suite, which enables real-time temperature images of the heated region to be acquired as the ultrasonic treatment is delivered. Using MRI thermometry during treatment, dynamic temperature feedback control over the intensity of the ultrasound beams and rotation of the Ultrasound Applicator can shape the pattern of thermal coagulation accurately and precisely in the prostate gland, thereby reducing the risk of possible damage to important surrounding anatomy such as the rectum, urinary sphincters, neurovascular bundles and pelvic bone. This coagulation method, therefore, has the potential to have lower complication rates than conventional therapies.

Inclusion Criteria:

• Male, age ≥45 and age ≤ 75 years
• Patient with low-risk, early-stage organ-confined prostate cancer (Stage T1c or T2a, N0, M0).
• Gleason score 6 (3+3) or max 7 (3+4)
• PSA ≤ 10 ng/ml
• Eligible for MR imaging (DOC-10252)

• Meets the following criteria on pre-treatment transrectal ultrasound imaging:

  1. No cysts or calcifications > 1.0 cm in size
  2. No evidence of extraprostatic extension or seminal vesicle invasion
  3. Overall prostate size less than 5 cm in sagittal length and less than 7 cm in diameter
• Biopsy confirmed adenocarcinoma of the prostate, performed at least 6 weeks prior to and no more than 6 months prior to the scheduled treatment.
• Eligible for General Anesthesia, as defined in American Society of Anesthesiologists (ASA)
• Normal rectal anatomy and rectal mucosa on digital rectal examination

Exclusion Criteria:

• Bleeding disorder (International Normalized Ratio (INR) > ULN and partial thromboplastin time (PTT) > ULN)
• Abnormal coagulation and current anticoagulant therapy. (Patients whose anticoagulation therapy can be temporarily reversed within 7 days prior to treatment delivery are eligible.)
• Acute or chronic Urinary Tract Infection (UTI)
• Interest in future fertility
• History of allergy to latex and any relevant medication
• History of any other malignancy other than skin cancer within the previous 5 years. Patients that have had a previous malignancy and no recurrence of that malignancy within the past 5 years will be allowed.
• Patients with peripheral arterial disease with intermittent claudication or Leriches Syndrome (i.e. claudication of the buttocks or perineum)
• Prior treatment of the prostate gland, including but not limited to radiation therapy (external beam or brachytherapy), high intensity focused ultrasound, thermal therapy, androgen deprivation therapy, bilateral orchiectomy, transurethral needle ablation of the prostate and transurethral resection of the prostate.
• Prior treatment with 5 alpha reductase inhibitor allowed provided it was for benign prostatic hypertrophy (not as prostate cancer treatment or prevention) and as long as drug has been stopped for at least 3 months
• History of any major rectal or pelvic surgery
• History of ulcerative colitis or other chronic inflammatory conditions affecting rectum (includes rectal fistula, anal stenosis, hemorrhoids)
• History of documented clinical prostatitis requiring therapy within previous 6 months
• History of urethral and bladder outlet disorders, including urethral stricture disease, urethral diverticulae, bladder neck contracture, urethral fistulae which had required prior urethrotomy, urethral stenting, urethroplasty or chronic indwelling urethral catheter
• Patients with artificial urinary sphincter or any penile implant (metallic or non-metallic)
• Neurologic bladder disorders
• Untreated bladder stones
• History of acute urinary retention
• Confirmed or suspected bladder cancer
• Urinary sphincter abnormalities
• Active untreated gross hematuria for any cause
• Post Void Residual (PVR) bladder volume > 250 mL
• Obstructing median lobe enlarged out of proportion to the rest of the prostate and protruding significantly into the bladder, sometimes referred to as "ball valve" median lobe.
• Received any prostate related investigational treatment within 12 months of Visit 1
• Undergone major surgery/surgical therapy for any cause within 1 month of Visit 1
• Prior pelvic radiotherapy
• Any of the following within the 6 months prior to Visit 1: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure (NYHA Class III or IV), cerebrovascular accident, transient ischemic attack, pulmonary embolism, sustained ventricular tachycardia, clinically significant bradycardia, ventricular fibrillation, or advanced heart block
• Ongoing cardiac dysrhythmias ≥ grade II (NCI CTCAE v4.0)
• History of Parkinson's disease or multiple sclerosis
• History of alcohol or drug abuse
• Treatment with antidepressant drugs
• Known immunosuppression
• Any serious illness or medical condition, including but not limited to: any uncontrolled infection, uncontrolled diabetes mellitus, or uncontrolled hypertension (> 150/100 mm Hg despite optimal medical therapy)
• Known infectious disease including HIV positivity or AIDS-related illness, HBV and HCV, or sexual transmitted diseases
• Pre-existing thyroid abnormality with thyroid function that cannot be maintained in the normal range with medication
• Current unilateral or bilateral hydronephrosis (confirmed by radiologic imaging within previous 12 months)

• Concurrent use:

  • Medications with anti-androgen properties (e.g. spironolactone, flutamide, ketoconazole, metronidazole, progestational agents)
  • Over the counter or herbal preparations such as cimetidine, saw palmetto , selenium (> 75 mcg) or vitamin E (> 100 IU)
  • Any investigational anabolic steroids or corticosteroids
  • Any investigational 5 alpha reductase inhibitors
• Treatment with drugs with dysrhythmic potential including terfenadine, quinidine, procainamide, diisopyramide, sotalol, probucol, bepridil, haloperidol, risperidone or indapamide
• Other severe, acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, which in the judgment of the investigator would make the patient inappropriate for entry into the this study.