A Phase 2, Randomized, Open Label, Parallel Arm Study to Evaluate the Safety and Efficacy of rAd-IFN/Syn3 Following Intravesical Administration in Subjects With High Grade, BCG Refractory or Relapsed Superficial Bladder Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 主要终点
- Incidence of High Grade-Recurrence Free Survival at 360 Days
研究概览
简要总结
This Phase 2 study is designed to assess the efficacy and safety of INSTILADRIN (rAd-IFN with Syn3) when given intravesically to patients with high grade non-muscle invasive bladder cancer who are refractory to or have relapsed from BCG therapy. The pharmacodynamics of INSTILADRIN will also be studied by measuring the interferon (IFNα2b) levels excreted in the urine. rAd-IFN is a non-replicating recombinant adenovirus type 5 (Ad5)-vector encoding the interferon alpha-2b (IFNα2b) gene. Syn 3 is clinical surfactant excipient which enhances the ability of the adenoviral vector to transfect cells in the bladder wall.
详细描述
Criteria for Evaluation:
Efficacy: A Response is defined as no evidence of recurrence of a high grade tumor by cystoscopy, cytology or if clinically indicated, biopsy.
Safety: The safety and tolerability of INSTILADRIN will be evaluated based on adverse event reports, vital signs, ECGs, clinical laboratory values and results of physical examination.
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
- Single (Participant)
盲法说明
The participant did not know if they received a high or low dose.
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
- •Aged 18 years or older at the time of consent
- •Able to give informed consent
- •Subjects with high grade BCG-refractory or relapsed NMIBC including
- •High grade non-invasive papillary carcinomas (Ta) and subjects with high grade tumors that invade sub-epithelial connective tissue (T1) or
- •Carcinoma in situ (CIS) only or
- •CIS and Ta or T1 tumors Refractory is defined as failure to achieve a disease-free state at six months after adequate induction of BCG therapy with either maintenance or re-induction at 3 months. Adequate induction is defined as a minimum of 5 out of 6 induction doses and adequate maintenance is defined as a minimum of 2 out of 3 doses of treatment.
- •Relapse is defined as recurrence within 1 year after a complete response to BCG treatment
- •Complete resection of visible papillary lesions or CIS by TURBT or endoscopic resection between 14 and 60 days prior to beginning study treatment
- •Available for the whole duration of the study
- •Life expectancy >2 years, in the opinion of the investigator
- •ECOG status 2 or less
- •Absence of upper tract urothelial carcinoma
- •Female subjects of childbearing potential must use maximally effective birth control during the period of therapy, must be willing to use contraception for 1 month following the last study drug infusion and must have a negative urine or serum pregnancy test upon entry into this study. Otherwise, female subjects must be postmenopausal (no menstrual period for a minimum of 12 months) or surgically sterile.
- •Male subjects must be surgically sterile or willing to use a double barrier contraception method upon enrollment, during the course of the study, and for 1 month following the last study drug infusion.
- •Adequate laboratory values.
- •Hemoglobin ≥10 g/dL.
- •WBC ≥4000/μL.
- •ANC ≥2000/μL.
- •Platelet count ≥100,000/μL.
- •INR within institutional normal limits.
- •aPTT within institutional normal limits.
- •AST ≤1.5 x ULN.
- •ALT ≤1.5 x ULN.
- •Total bilirubin within institutional normal limits.
- •Creatinine ≤1.5 x ULN.
排除标准
- •Current or previous evidence of muscle invasive or metastatic disease
- •Current systemic therapy for bladder cancer
- •Current or prior pelvic external beam radiotherapy
- •Prior treatment with adenovirus-based drugs
- •Suspected hypersensitivity to interferon alpha
- •Existing urinary tract infection or bacterial cystitis
- •Clinically significant and unexplained elevated liver or renal function tests
- •Women who are pregnant or lactating
- •Severe cardiovascular disease
- •History of malignancy of other organ system within past 5 years (except treated basal cell carcinoma or squamous cell carcinoma of the skin)
- •Subjects who cannot hold instillation for 1 hour
- •Subjects who cannot tolerate intravesical dosing or intravesical surgical manipulation
- •Intravesical therapy within 6 weeks of enrollment
研究组 & 干预措施
rAd-IFN Dose 1x10^11vps/ml
Subjects will be randomly assigned to one of two INSTILADRIN arms.
干预措施: INSTILADRIN (Drug)
rAd-IFN dose 3x10^11 vps/ml
Subjects will be randomly assigned to one of two INSTILADRIN arms.
干预措施: INSTILADRIN (Drug)
结局指标
主要结局
Incidence of High Grade-Recurrence Free Survival at 360 Days
时间窗: 360 Days
Following the initial treatment, patients were clinically evaluated and re-treated at the Days 90, 180, and 270 time points, as outlined below. The decision to repeat treatment was determined by the clinical response observed following the previous treatment(s). Patients were assessed for High-Grade disease recurrence by cytology, cystoscopy and, if clinically indicated, biopsies were performed to obtain accurate staging. If no evidence of recurrence of High-Grade disease was detected, then a further dose of rAd-IFN/Syn3 was administered as maintenance therapy. Patients who had recurrence of High-Grade disease were withdrawn from treatment but were followed for survival and time to cystectomy. At 360 Days, a final efficacy evaluation was performed for patients receiving 4 doses of drug. This included cystoscopy, cytology, and biopsy.
次要结局
- Incidence of Cystectomy in All Patients(360 Days)
- Overall Survival in All Patients.(360 Days)
- Safety of rAd-IFN/Syn3(360 Days)
- Incidence of High Grade Recurrence-Free Survival at 3 Months (90 Days).(90 Days)
- Incidence of High Grade-Recurrence-Free Survival at 6 Months (180 Days).(180 Days)
- Incidence of High Grade-Recurrence-Free Survival at 9 Months (270 Days).(270 Days)
- Number of Patients With Elevated Levels of Viral Vector in Blood(103 Days)
- Number of Patients With Elevated Levels of Viral Vector in Urine(103 Days)
- Number of Patients With Elevated IFN alpha2b Protein Levels in Serum(360 Days)
- Number of Patients With Elevated IFN alpha2b Protein Levels in Urine(103 Days)
- Number of Patients With Elevated Levels of Anti-IFN alpha2b Antibodies in Serum(360 Days)
- Number of Patients With Elevated Levels of Anti-Adenovirus Type 5 Antibodies in Serum.(360 Days)