Effect of Neoadjuvant Degarelix on MRI-guided Transurethral Ultrasound Ablation (TULSA) in Patients with Intermediate-risk Prostate Cancer: a Pilot Study
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- Change in prostate tumor volume after neoadjuvant ADT
研究概览
简要总结
Clinical studies have shown that magnetic resonance imaging-guided transurethral ultrasound ablation (TULSA) of the prostate is safe and effective. In the TULSA procedure, prostate tissue is killed by heating with ultrasound. This clinical trial explores if adding drug therapy with Degarelix before TULSA has the potential to improve further the effectiveness of TULSA in the treatment of localized prostate cancer, especially for patients with more aggressive diseases.
详细描述
Androgen deprivation therapy (ADT) has been shown to reduce prostate and tumor size. In this study, magnetic resonance imaging (MRI) is used to investigate the effect of Degarelix ADT on the properties of prostate tissue that can affect the heating of the tissues in the TULSA procedure. The main goal is to find out if ADT can change the tissue structure in a way that improves the ability of the TULSA procedure to heat tissues and better kill the diseased tissue, reducing the chance of the disease reoccurring. ADT and the TULSA procedure can help patients with more aggressive diseases avoid the adverse effects associated with surgery or radiation therapy. Specific objectives are:
- To measure the change in prostate and tumor size, tissue structural changes, and the blood flow within the prostate after ADT.
- To measure the distribution of heating over the prostate after TULSA treatment.
- To evaluate complications and genitourinary function and quality of life with patient-reported outcome measures.
- To evaluate local cancer control and longer-term oncological outcomes after combination therapy of neoadjuvant ADT and TULSA treatment.
About 15 subjects will participate. Each will receive Degarelix for three months, followed by whole-prostate gland TULSA treatment, and be followed for five years. Throughout the study, subjects will receive MRI scans and complete questionnaires regarding functional status and quality of life to understand the side effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male age ≥ 40 years and candidate for radical prostate cancer treatment
- •Estimated life expectancy > 8 years
- •At least one MRI-visible and biopsy-concordant tumor defined as Prostate Imaging-Reporting and Data System v2 (PI-RADS v2.1) ≥ 3
- •Biopsy-confirmed, intermediate-risk localized prostate cancer:
- •Clinical or radiological tumor stage ≤ T2c, N0, M0
- •ISUP GG 2 or 3
- •Biopsy obtained ≥ 6 weeks and ≤ 12 months before treatment
- •PSA ≤ 20 ng/ml
- •No prior definitive treatment of prostate cancer
- •Eligible for MRI
- •Eligible for general anesthesia (American Society of Anesthesiologists Class III or less)
- •Patients taking 5-alpha reductase inhibitors (5-ARIs) are eligible if use is discontinued three months before and throughout the study period.
- •Informed consent: The patient must speak Finnish, English, or Swedish and must be able to understand the meaning of the study. The patient must be willing and able to sign the appropriate Ethics Committee (EC) approved informed consent documents in the presence of the designated staff.
排除标准
- •Prior prostate cancer treatment with chemotherapy or hormonal therapy, including chemical or surgical castration, antiandrogen therapy, or androgen-receptor signaling inhibitors.
- •Relative or absolute contraindication to Degarelix
- •Severe, active cardiovascular comorbidity including unstable angina pectoris, congestive heart failure, deep vein thrombosis, pulmonary embolism, or myocardial infarction within the last six months.
- •Inability to undergo MRI due to claustrophobia or contraindications (cardiac pacemaker, intracranial clips, etc.)
- •Severe kidney failure as determined by estimated glomerular filtration rate (eGFR) less than 30 ml/min per 1.73 m2
- •Prostate calcifications obstructing the planned ultrasound beam path in the line of sight of the MRI visible tumor
- •Prostate cysts at the prostate capsule within the planned ultrasound beam path in the line of sight of the MRI visible tumor
- •Evidence of extraprostatic disease based on imaging (MRI, bone scintigraphy, single-photon emission tomography, computed tomography, prostate-specific membrane antigen-positron emission tomography [PSMA-PET]) or histopathology
- •History of chronic inflammatory conditions (e.g., inflammatory bowel disease) affecting the rectum (also includes rectal fistula and anal/rectal stenosis)
- •Hip replacement surgery or other metal in the pelvic area
- •Known allergy or contraindication to gadolinium or gastro-intestinal anti-spasmodic drug glucagon
- •Concomitant treatment with medications contraindicated to Glucagen used as antispasmolytic agent during TULSA treatment (e.g., Feochromocytoma)
- •Any other conditions that might compromise patient safety, based on the clinical judgment of the responsible urologist
- •Another primary malignancy unless disease-free survival is > 8 years
研究组 & 干预措施
3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation
After three months of neoadjuvant ADT with Degarelix, the subject will undergo whole-prostate gland MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) treatment.
干预措施: Degarelix (Drug)
3-month neoadjuvant Degarelix followed by whole-gland MRI-guided transurethral ultrasound ablation
After three months of neoadjuvant ADT with Degarelix, the subject will undergo whole-prostate gland MRI-guided transurethral ultrasound ablation (TULSA) (TULSA-PRO, Profound Medical Inc., Toronto, Canada) treatment.
干预措施: MRI-guided transurethral ultrasound ablation (TULSA) (Device)
结局指标
主要结局
Change in prostate tumor volume after neoadjuvant ADT
时间窗: Baseline and four, eight, and 12 weeks of ADT.
The prostate tumor volume change will be determined by comparing the prostate tumor volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
The frequency and severity of adverse events
时间窗: Every follow-up visit until the first year of follow-up.
The frequency and severity of adverse events after neoadjuvant Degarelix and TULSA treatment will be determined by using the CTCAE v6.0 classification. Adverse events attributed to TULSA will also be graded using the Clavien Dindo classification for surgical complications.
Change in prostate volume after neoadjuvant ADT
时间窗: Baseline and four, eight, and 12 weeks of ADT.
The prostate volume change will be determined by comparing the prostate volume measured on T2-weighted MRI at four, eight, and 12 weeks of ADT to that at baseline.
次要结局
- Change in prostate vascular perfusion after neoadjuvant ADT(Baseline and four, eight, and 12 weeks of ADT.)
- Change in prostate tumor vascular perfusion after neoadjuvant ADT(Baseline and four, eight, and 12 weeks of ADT.)
- Thermal coverage after whole-prostate gland TULSA(Immediately after the TULSA procedure.)
- Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT(Baseline and 12 weeks of ADT.)
- The frequency and severity of adverse events during extended follow-up(Every follow-up visit until the five years of follow-up.)
- Metastasis-free, prostate cancer-specific, and overall survival(One, three and five years after the TULSA procedure.)
- Change in quality of life (QoL) and functional status outcomes after neoadjuvant ADT and whole-prostate gland TULSA(Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.)
- Change in lower urinary tract symptoms after neoadjuvant ADT and whole-prostate gland TULSA(Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.)
- Change in prostate tumor-capsule contact length after neoadjuvant ADT(Baseline and four, eight, and 12 weeks of ADT.)
- Change in erectile function after neoadjuvant ADT and whole-prostate gland TULSA(Baseline and 12 weeks of ADT, and three, six, 12, 36 and 60 months after the TULSA procedure.)
- Salvage therapy-free survival(Every post-TULSA follow-up visit until the five years of follow-up.)
- Biochemical failure-free survival(One, three, and five years after the TULSA procedure.)
- Freedom from biopsy-proven clinically-significant prostate cancer(Twelve months after the TULSA procedure)
- Freedom from any biopsy-proven prostate cancer(Twelve months after the TULSA procedure)
- Change in lower urinary tract symptoms after neoadjuvant ADT(Baseline and 12 weeks of ADT.)
- Failure-free survival(Every post-TULSA follow-up visit until the five years of follow-up.)
- Change in periprostatic, prostate and tumor tissue structures after neoadjuvant ADT(Baseline and four, eight, and 12 weeks of ADT.)
- Change in erectile function after neoadjuvant ADT(Baseline and 12 weeks of ADT.)
- Systemic therapy-free survival(Every post-TULSA follow-up visit until the five years of follow-up.)