Evaluation of Efficacy of TOOKAD® (VTP) Versus Active Surveillance for Intermediate Risk Localized Prostate Cancer

Multi-center, prospective, randomized controlled clinical trial that will compare two treatment methods (PGA with TOOKAD® VTP and Active Surveillance) for treating localized prostate cancer. The study will include criteria for evaluation, biopsy, eligibility, informed consent, subsequent management and decision making conducted based on data provided locally at each center that follow a set of standardized criteria.

The primary endpoint requires follow-up through 30 months, but all subjects will be followed for 72 months regardless of initiation of other local or systemic prostate cancer treatments, which will allow assessments of recurrence rates and morbidity after conversion to radical therapy, long-term safety and tolerability, as well as oncologic outcomes.

This is multi-center, prospective, randomized controlled phase III clinical trial that will compare two treatment methods (PGA with TOOKAD® VTP and Active Surveillance) for treating localized prostate cancer who meet the inclusion criteria will be approached for participation in the clinical study. Patients consenting to participate will be individually randomized to TOOKAD® VTP or Active Surveillance with a 1:1 ratio. Central randomization will be performed using an independent web-based allocation system. Randomization will be stratified by center using minimization. Ongoing assessment of patients in both arms will be balanced, including follow up examinations, PSA testing, MRI and biopsies at defined intervals.

Subjects in the experimental arm will receive the experimental treatment consisting of unilateral TOOKAD® VTP treatment applied to the index lobe containing pattern 4 cancer. The treatment will be administered under general anesthesia. Routine ultrasound examination in the operating room will be performed for morphometric description of the prostate and to facilitate accurate treatment planning and probe placement. Ultrasound will not be used for diagnostic purposes.

Eligibility Criteria:
Inclusion Criteria:

1. Men 18 years or older.
2. Men who have chosen Active Surveillance as the treatment for their prostate cancer.
3. Patients who have had a multiparametric MRI of the prostate performed and have undergone transrectal systematic biopsy plus biopsy of any lesions (or "areas") considered suspicious per the MRI (PIRADS version 2 score of 4 or 5) within 6 months before signing consent.
4. Unilateral Grade Group 2 (Gleason grade 3+4=7) prostate cancer with a total length of Gleason pattern 4 no more than 2mm when measured in all systematic biopsy cores plus up to 1 core from each targeted biopsy lesion (if more than 1 core is taken from a given lesion the core with the longest length of pattern 4 will be included). Note: the presence and length of Grade Group 1 (Gleason score 3+3=6) cancer in the biopsy will not be considered when determining eligibility.
5. Prostate cancer clinical stage up to cT2a, N0/Nx, M0/Mx.
6. Prostate volume ≥20 mL and ≤80 mL
7. Serum PSA ≤10 ng/mL.
8. Patients with cT2a and PSA between 10 and 20 ng/mL will have appropriate imaging and work up to sufficiently exclude clinical evidence of bone metastases (e.g., bone scan, whole body MRI, PET scan, or equivalent). Patients with sites considered "suspicious" may be evaluated with confirmatory biopsy to determine eligibility. Patients with sites considered "definite" or "consistent with" bone metastases will be excluded.
9. Men who are sexually active with women of childbearing potential must use contraceptive method with a failure rate of less than 1% per year. Contraception should be continued for a period of 90 days after the VTP procedure. The individual methods of contraception may be determined in consultation with the investigator.
10. Signed Informed Consent Form.

Exclusion Criteria:

1. Grade Group 3, 4 or 5 (≥ Gleason Score 4+3=7) cancer
2. In patients with Grade Group 2 cancers, a total length of Gleason pattern 4 more than 2mm when measured in all systematic biopsy cores plus up to 1 core from each targeted biopsy lesion (if more than 1 core is taken from a given lesion, include the mm of pattern 4 in the 1 core with the longest length of pattern 4)
3. Bilateral GG 2 cancer
4. MRI evidence of extracapsular extension of cancer (MRI read as "definite", "frank" or "gross" ECE, or MRI lesion with \>10mm capsular contact, in an area with biopsy proven cancer).
5. Seminal vesicle invasion on DRE or MRI ("probable" or "consistent with")
6. Radiographically suspicious lymph node involvement confirmed with biopsy or PET scan.
7. Any prior or current treatment for prostate cancer, including but not limited to surgery, radiation therapy (external or brachytherapy) or chemotherapy;
8. Life expectancy less than 10 years;
9. Participation in another clinical study involving an investigational product that in the opinion of the investigator may interfere with the endpoints or investigational criteria of this study;
10. Inability to understand the informed consent document, to give consent voluntarily or to complete the study tasks, especially inability to understand and fulfill the health-related QOL questionnaire;
11. Any history of a definitively ablative procedure for benign prostatic disease, such as benign prostatic hyperplasia, including TURP, whether electrosurgical or thermal laser ablation; or high intensity frequency ultrasound (HIFU) or cryotherapy, for focal or total ablative therapy of the prostate.
12. Any condition or history of illness or surgery that may pose an additional risk to men undergoing the VTP procedure such as:

    1. Medical conditions that preclude the use of general anesthesia;
    2. Any condition or history of active rectal inflammatory bowel disease or other factors which might increase the risk of fistula formation;
    3. Hormonal manipulation (excluding 5-alpha-reductase inhibitors) that alters androgen production within the previous 6 months;
    4. Oral anticoagulant drugs that could not be withdrawn at least 5 days prior to the VTP procedure or antiplatelet drugs (e.g. aspirin) that could not be withdrawn at least 5 days prior to the VTP procedure and for at least 3 days after VTP;
    5. Renal and hepatic disorders with values of \>1.5 times the upper limit of normal (ULN) or blood disorders (upon clinician judgment);
    6. A history of sun hypersensitivity or photosensitive dermatitis.
    7. Any other condition or history of illness or surgery that in the opinion of the investigator might affect the conduct and results of the study or pose additional risks to the patient (e.g., cardiac or respiratory disease precluding general anesthesia, active urethral stricture disease).