A Multicenter, Single-Arm Study Evaluating the Efficacy of Synergo® Radiofrequency-Induced Thermochemotherapy Effect With Mitomycin C in Non-Muscle Invasive Bladder Cancer Patients With BCG-refractory CIS
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 主要终点
- Recurrence-free survival
研究概览
简要总结
This multicenter, prospective, single-arm, phase 3 study will assess the proportion of disease-free patients, starting from administration of the first study treatment to at least 12-months after the first treatment, and up to 2 years (the latter only in patients choosing to participate in longer-term disease-free-survival data collection).
详细描述
The study will consist of three periods: 1) Screening; 2) Induction, and 3) Maintenance treatment and follow-up.
Screening period After signing informed consent, patients will be screened for study eligibility by assessment of inclusion and exclusion criteria. Screening procedures will include collection of demographic data, medical history, physical examination, vital signs, and laboratory evaluations.
Induction period Patients will receive 8 weekly treatments of RITE + MMC, using the Synergo® System. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. These 8 treatments will be followed by a pause (see Table 1), after which a follow-up cystoscopy (first follow-up control) will be conducted during Weeks 12-13 (from the first treatment).
Maintenance Treatment and Follow-up Period
During the maintenance period, patients will receive one Synergo® RITE + MMC treatment every 6 weeks. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. Maintenance treatments will be given until the end of 12 months after the patient's first induction treatment, unless the patient's participation in the study is terminated due to either:
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with CIS, with or without coexisting papillary NMIBC, who either:
- •fail to achieve a disease-free status by 6 months after initial BCG therapy, with maintenance or re-induction at 3 months due to either persistent or rapidly recurrent disease, or
- •experience a worsening in NMIBC state following initial BCG therapy presenting with a new NMIBC instance, other than TaLG.
- •All clinical, intra-operative and pathological items for the EAU risk stratification must be documented including a bladder map.
- •Patients with papillary disease must have undergone a repeat TUR:
- •if the initial TUR was incomplete.
- •if there was no muscle in the specimen after the initial TUR (except in TaLG tumors).
- •in all T1 tumors. TUR of T1 sites must include muscle.
- •in all HG tumors > 3cm.
- •CT-IVU or IVU confirmation of absence of tumor(s) in the upper tract, kidney and ureters performed within 6 months before the treatment initiation in selected cases as recommended in latest EAU guidelines published prior to screening. If IVU protocol not available or contrast allergy/poor renal function preclude such imaging, then non-contrast CT or MRI of the abdomen/pelvis within the same timeframe will suffice.
- •Visual inspection to exclude urothelial carcinoma (UC) in the urethra during cystoscopy.
- •Biopsy of the prostatic urethra in male patients prior to recruitment to exclude UC of the prostatic urethra, in patients with:
- •tumor of trigone,
- •tumor of bladder neck, or
- •abnormal prostatic urethra
- •All patients must have urine cytology collected from either voided urine or bladder wash within the screening period prior to recruitment.
- •All patients must have prostatic urethral biopsies collected within the screening period prior to recruitment.
- •Age ≥ 18 yrs.
- •Normal kidneys and ureters.
- •Pre-treatment hematology and biochemistry values within the limits:
- •Hemoglobin ≥ 10 g/dl
- •Platelets ≥ 150 x 10^9/L
- •WBC ≥ 3.0 x 10^9/L
- •ANC ≥ 1.5 x 10^9/L
- •Serum creatinine < 1.5 x ULN
- •SGOT < 1.5 x ULN
- •SGPT < 1.5 x ULN
- •Alkaline phosphatase < 1.5 x ULN
- •Negative pregnancy test for women of childbearing potential.
- •A life expectancy at least of the duration of the study (up to 13 months).
- •Patients unfit or unwilling to have a full or partial (if appropriate) cystectomy.
- •Signed informed consent.
排除标准
- •Non-UC tumor of the urinary tract.
- •Upper tract and intramural tumors (e.g., in ostium).
- •Positive selective cytology from the upper tract.
- •History of stage > T1 UC.
- •Papillary tumor in repeat TUR in patients diagnosed with HG > 3cm and/or T1 in the initial TUR.
- •Papillary tumor ≥ T1 in repeat TUR
- •Known or suspected reduced bladder capacity. Patients will have a US estimation of maximum bladder capacity or void spontaneously the maximum they can retain in their bladder, and this will be used to determine urine volume. A minimum volume of 250 ml is required.
- •Bleeding disorder.
- •Macrohematuria of ≥ 250 RBC/uL or equivalent (e.g., > "+++" erythrocytes in a dipstick analysis) within 4 weeks before treatment start.
- •Lactating women.
- •Women of childbearing potential unwilling or unable to use adequate contraception if sexually active.
- •More than a maintenance dose of oral corticosteroids (maintenance dose is defined as the same dose regimen over the past 6 months for a condition requiring continual corticosteroid treatment) or patients with an immunocompromised state for any reason.
- •More than low-dose methotrexate (>17.5 mg once a week).
- •Other malignancy within the past 5 years, except: non-melanomatous skin cancer cured by excision, surgically treated carcinoma in situ of the cervix or ductal CIS (DCIS)/lobular CIS (LCIS) of the breast or stable prostate cancer (under active surveillance or hormone control) with a life expectancy of more than 5 years.
- •Any known allergy (e.g., to MMC) or adverse event that would prevent a prospective study participant from receiving the study treatment.
- •Known untreated urethral strictural disease or bladder neck contracture or any other condition that may prevent catheterization with 21F catheter. Patients may undergo dilation or urethral incision before entering the study.
- •Bladder diverticula with cumulative diameter > 1cm or tumor in a diverticulum.
- •UTI at any time within 4 weeks before treatment start.
- •Significant urinary incontinence (spontaneous, requiring use of pads).
- •History of pelvic irradiation.
- •Patients with implanted electronic devices (such as cardiac pacemakers) unless they receive permission from their treating physician (e.g., cardiologist) and are monitored by a treating physician during the treatment session.
- •Participation in another study, unless discussed with and approved by the study manager.
研究组 & 干预措施
Synergo® RITE + MMC
Induction
Patients will receive 8 weekly treatments of Synergo® RITE + MMC, using the Synergo® System. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. These 8 treatments will be followed by a pause (see Table 1), after which a follow-up cystoscopy (first follow-up control) will be conducted during Weeks 12-13 (from the first treatment).
Maintenance
Patients will receive one Synergo® RITE + MMC treatment every 6 weeks. Each treatment lasts about 60 minutes and consists of two 30-minute cycles with 40 mg MMC/50 ml sterile water for injection each cycle. Maintenance treatments will be given until the end of 12 months after the patient's first induction treatment.
干预措施: Synergo® RITE + MMC (Device)
结局指标
主要结局
Recurrence-free survival
时间窗: 12 months
The study will be deemed successful if the recurrence-free survival probability after 12 months is at least 30%.
次要结局
- Complete Response Rate (CRR)(6 months after first treatment)
- Proportion of patients who discontinue treatment for safety reasons.(12 months)
- Rate of serious adverse events(12 months)