An Evaluation of the Efficacy of Partial Gland Ablation (PGA) With TOOKAD® Vascular Targeted Photodynamic Therapy (VTP) Versus Active Surveillance for Men With Intermediate Risk Localized Prostate Cancer
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Rate of objective progression
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Men 18 years or older.
- •Men who have chosen Active Surveillance as the treatment for their prostate cancer.
- •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.
- •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.
- •Prostate cancer clinical stage up to cT2a, N0/Nx, M0/Mx.
- •Prostate volume ≥20 mL and ≤80 mL
- •Serum PSA ≤10 ng/mL.
- •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.
- •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.
- •Signed Informed Consent Form.
排除标准
- •Grade Group 3, 4 or 5 (≥ Gleason Score 4+3=7) cancer
- •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)
- •Bilateral GG 2 cancer
- •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).
- •Seminal vesicle invasion on DRE or MRI ("probable" or "consistent with")
- •Radiographically suspicious lymph node involvement confirmed with biopsy or PET scan.
- •Any prior or current treatment for prostate cancer, including but not limited to surgery, radiation therapy (external or brachytherapy) or chemotherapy;
- •Life expectancy less than 10 years;
- •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;
- •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;
- •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.
- •Any condition or history of illness or surgery that may pose an additional risk to men undergoing the VTP procedure such as:
- •Medical conditions that preclude the use of general anesthesia;
- •Any condition or history of active rectal inflammatory bowel disease or other factors which might increase the risk of fistula formation;
- •Hormonal manipulation (excluding 5-alpha-reductase inhibitors) that alters androgen production within the previous 6 months;
- •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;
- •Renal and hepatic disorders with values of >1.5 times the upper limit of normal (ULN) or blood disorders (upon clinician judgment);
- •A history of sun hypersensitivity or photosensitive dermatitis.
- •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).
研究组 & 干预措施
TOOKAD®
TOOKAD® , lyophilized formulation, given at a dose of 4mg/Kg.
干预措施: TOOKAD® (Drug)
结局指标
主要结局
Rate of objective progression
时间窗: over 30 months
To evaluate the difference in the rate of objective progression of cancer between men treated with TOOKAD -VTP and men managed with Active Surveillance for localized prostate cancer.
次要结局
- Rate of conversion to radical local or systemic therapy(over 30 and 72 months)
- Rate of conversion to radical local or systemic therapy following objective progression(over 30 and 72 months)
- Adverse events and Serious Adverse events(Screening-Month 72)
- FACT-P - Question GP5 - Bother Related to Adverse Events(Screening,Week 2, Week 4, Week 6, Week 8, Month 3, Month 4, Month 5, Month 6, Month 12, Month 18, Month 24, and Month 36)
- Bowel Symptoms: PRO-CTCAE questions 17 and 18(Screening,Week 4, Week 8, Month 3, Month 6, Month 12, Month 18, Month 24, and Month 36, Month 48, Month 60, and Month 72)
- Safety of radical, local or systemic treatment(within 90 days after treatment)
- Rate of biopsy progression in the index lobe(at 30 and 72 months)
- Rate of clinical local or distant progression(Screening,Month 12, Month 24,Month 42 and Month 60)
- Urinary:PRO-CTCAE - Urinary Questions 61 - 65(Screening,Week 2, Week 4, Week 6, Week 8, Month 3, Month 4, Month 5, Month 6, Month 12, Month 18, Month 24, and Month 36)
- Pain: PRO-CTCAE Pain Question 48(Screening,Week 2, Week 4, Week 6, Week 8, Month 3, Month 4, Month 5, Month 6, Month 12, Month 18, Month 24, and Month 36)
- Assessment of PSA density(Screening, Day of VTP ,Month 6, Month 18, Month 30, Month 36, Month 48 and Month 72)
- Anxiety = PRO-CTCAE question 54(Screening,Week 4, Week 8, Month 3, Month 6, Month 12, Month 18, Month 24, and Month 36, Month 48, Month 60, and Month 72)
- Anxiety = MAX-PC Questions 15-18 - Anxiety related to fear of prostate cancer recurrence(Screening,Month 6, Month 12, Month 18, Month 24, and Month 36, Month 48, Month 60, and Month 72)
- Assessment feasibility of performing radical, local or systemic treatment(within 90 days after treatment)
- Clinical recurrence(6 weeks and 24 months after treatment)
- Assessment of MRI dynamic characteristics (Development of new lesions)(Month 12,Month 24, Month 42 and Month 60)
- Sexual Function: PRO-CTCAE questions 66-68 and 70-72(Screening,Week 4, Week 8, Month 3, Month 6, Month 12, Month 18, Month 24, and Month 36, Month 48, Month 60, and Month 72)
- Assessment of PSA kinetics(Screening, Day of VTP ,Month 6, Month 18, Month 30, Month 36, Month 48 and Month 72)
- Assessment of MRI dynamic characteristics (change in PIRADS v2 score of initial lesions)(Screening, Month 12,Month 24, Month 42 and Month 60)
- Assessment of MRI dynamic characteristics (Changes in level of suspicion for ECE, SVI, LN metastases)(Screening, Month 12,Month 24, Month 42 and Month 60)
- Biochemical outcomes of radical, local or systemic treatment(6 weeks and 24 months after treatment)
- Assessment of MRI dynamic characteristics (change in size of initial lesions)(Screening, Month 12,Month 24, Month 42 and Month 60)
- Primary cause for conversion to radical treatment(Over 30 and 72 months)
- Assessment of PSA Level(Screening, Day of VTP ,Month 6, Month 18, Month 30, Month 36, Month 48 and Month 72)