Neoadjuvant Intravesical NIS Measles Virus (MV-NIS) in Patients Undergoing Cystectomy for Urothelial Carcinoma But Ineligible for Neoadjuvant Cisplatin-based Chemotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Vyriad, Inc.
- 入组人数
- 8
- 试验地点
- 6
- 主要终点
- Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03)
研究概览
简要总结
This is a Phase 1 study designed to test the tolerability and feasibility of intravesical therapy with an attenuated Measles virus (MV-NIS) in patients with urothelial carcinoma who are undergoing radical cystectomy but are ineligible or do not desire neoadjuvant chemotherapy.
详细描述
Study VYR-MV1-102 is a Phase 1 study designed to determine the tolerability, feasibility and preliminary efficacy of attenuated MV-NIS virus after neoadjuvant intravesical administration prior to RC in patients with UC who are ineligible for current neoadjuvant chemotherapy.
Investigators will use a novel adaptive trial design that varies the time between TURBT, virus administration and RC.
Currently, intravesical administration of BCG is delayed four to six weeks after TURBT to reduce the likelihood of systemic BCG absorption and BCG sepsis. Given this clinical safety precedent, Investigators propose initial patients be treated within one week of RC to maximize the time between TURBT and MV-NIS administration.
Subsequent patients will be treated earlier before RC (up to 29 days prior), thereby reducing the interval between TURBT and virus administration to maximize the treatment duration before RC. An expansion cohort will also be used to test the feasibility, tolerability and efficacy of two repeat MV-NIS doses prior to RC. MV-NIS has been proven safe at a dose of 1x1011 TCID50 intravenously in patients lacking MV immunity (Russell 2014), which allays concern for systemic toxicity after intravesical administration even if post-TURBT administration results in systemic MV-NIS absorption.
Pathologic downstaging and CR (assessed by T0 rate) at surgery are secondary endpoints, designed to give an early indication of efficacy potential. This will facilitate future virotherapy strategies targeting replicative tumor destruction and stimulation of systemic anti-tumor immunity as possible strategies for neoadjuvant and bladder-sparing therapy.
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
- •Diagnosis of Urothelial carcinoma (UC) of the bladder, with histologic confirmation of primary UC pathology; indication for Radical cystectomy (RC); ineligibility for platinum-based neoadjuvant chemotherapy
- •ECOG Performance Status (PS) 0 or
- •Ability to provide informed consent.
- •Willingness to comply with all required protocol procedures including providing biologic specimens and returning to the clinical study site for follow up visits.
- •Performance status sufficient to undergo RC (in the opinion of the enrolling urologist) including adequate hematological, liver and kidney function
- •Must be willing to implement contraception throughout study and for 30 days following RC.
排除标准
- •Variant UC pathology including but not limited to micropapillary, signet ring,sarcomatoid, and clear cell variants.
- •Patients with any other prior malignancy are not allowed except for the following: History of or concurrent non-invasive UC involving a portion of urinary tract outside of the bladder; Adequately treated basal cell or squamous cell skin cancer; In situ cervical cancer; Adequately treated Stage I or II cancer from which the patient is currently incomplete remission or other cancer from which the patient has been disease-free for 2 years.
- •Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways.
- •Any of the following prior therapy: Chemotherapy ≤ 3 weeks prior to registration. Biologic therapy ≤ 4 weeks prior to registration. Radiation therapy ≤ 3 weeks prior to registration
- •Other concurrent investigational therapy (utilized for a non-FDA-approved indication and in the context of a research investigation).
- •Pregnant women.
- •Nursing women.
- •Men or women of childbearing potential who are unwilling to employ adequate contraception during treatment and 8 weeks following the completion of study drug treatment.
- •Allergy to measles vaccine or history of severe reaction to prior measles vaccination.
- •History of organ transplantation.
结局指标
主要结局
Number of participants with intravesical MV-NIS treatment related adverse events (NCI CTCAE; Version 4.03)
时间窗: 30 days after cystectomy
Assessment of safety and toxicity of intravesical MV-NIS administration in patients with Urothelial Carcinoma undergoing cystectomy
次要结局
- Pathologic staging at time of cystectomy following intravesical MV-NIS therapy(Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration))
- pT0 rate at time of cystectomy following intravesical MV-NIS therapy(Measured in bladder specimen following cystectomy (up to 29 days following MV-NIS administration))