A First In Human Phase I Trial Evaluating Safety, Tolerability and Response of [211At]At-Girentuximab (ATO-101™) in Patients With Non-Muscle-Invasive Bladder Cancer Refractory to Standard Treatment
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- To determine the Maximum Tolerated Dose (MTD) of ATO-101™.
研究概览
简要总结
Non-Muscle-Invasive Bladder cancer (NMIBC) tumours often recur despite TransUrethral Resection of Bladder (TURB) and Bacillus Calmette-Guerin (BCG) intravesical instillations, and have no effective conservative treatment options. Alpha emitters like Astatine-211 (211At), due to their short path and short half-life, show promise for superficial targets such as NMIBC.
Carbonic anhydrase IX (CAIX), overexpressed in 70-90% of NMIBC cases but absent in healthy tissues, is an ideal target.
A clinical feasibility Positron emission tomography-computed tomography (PET/CT) imaging study (Pertinence, NCT04897763) was conducted at Institut de cancérologie Ouest (ICO) in six patients using Girentuximab labelled with Zirconium-89 ([89Zr]Zr-girentuximab). It demonstrated successful tracer targeting and no radioactive leakage beyond the bladder following intravesical instillation. The study also confirmed the absence of toxicity, contamination, or significant additional staff radiation exposure.
ATO-101™ ([²¹¹At]At-girentuximab) could enable localised tumour destruction while preserving the bladder in patients with BCG-unresponsive NMIBC. The ongoing First In Human (FIH) study evaluate the safety of ATO-101™ in patients with BCG-unresponsive NMIBC.
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
- •Performance Status (PS): 0 or
- •Patient experiencing relapse following standard treatment (BCG therapy with or without Mitomycin), before radical surgery which is being considered as a therapeutic option.
- •Clinical evidence of NMIBC based on cystoscopy and proven histologically of papillary tumours.
- •Histologically confirmed bladder cancer patients relapsing without muscle invasion.
- •Negative serum/urine pregnancy test prior to ATO-101™ administration for female patient of childbearing potential.
- •Consent to use a contraception method for at least 3 months after administration of ATO-101™.
- •Adequate organ function confirmed by laboratory tests results allowing for safe administration of ATO-101™.
排除标准
- •Patient with urinary incontinence.
- •Patient treated with anticoagulant or platelet antiaggregant therapies.
- •Symptoms of urine infection.
- •Patient with urethral stenosis.
- •Patient with valvular heart disease.
- •No history of congestive heart failure.
- •Known hypersensitivity to Girentuximab.
- •Exposure to any experimental diagnostic or therapeutic drug within 30 days prior the date of planned administration of ATO-101™.
- •Serious non-malignant disease that may interfere with the objectives of the study or with the safety or compliance of the patient as judged by the investigator.
- •Concomitant cancer in the past 5 years except cutaneous cancers (except melanoma) and in situ carcinoma in past 3 years.
- •Prior chemotherapy, radiotherapy (other than short cycle of palliative radiotherapy), immunotherapy within 21 days of ATO-101™ administration.
- •Pregnant or likely to be pregnant or nursing patient.
研究组 & 干预措施
ATO-101™
[211At]At-Girentuximab (ATO-101™) intravesical administration
干预措施: ATO-101™ (Drug)
结局指标
主要结局
To determine the Maximum Tolerated Dose (MTD) of ATO-101™.
时间窗: 15 days
The primary endpoint is the occurrence of dose-limiting toxicities (DLTs) during the DLT observation period.
To determine the Recommended Dose for Expansion (RDE) of ATO-101™.
时间窗: 15 days
The primary endpoint is the occurrence of dose-limiting toxicities (DLTs) during the DLT observation period.
次要结局
未报告次要终点