A Phase Ⅰ, Open Label, Multi-center Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of RAG-01 in Patients With Non-muscle-invasive Bladder Cancer (NMIBC) Who Have Failed Bacillus Calmette Guérin (BCG) Therapy
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 72
- 试验地点
- 3
- 主要终点
- Safety and tolerability of RAG-01 in patients with non-muscle-invasive bladder cancer (NMIBC)
研究概览
简要总结
This is an open label, multi-center study to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of RAG-01 in patients with NMIBC who have failed BCG therapy.
详细描述
This study includes a dose escalation and a dose expansion. The dose escalation part will adopt a '3+3' dose escalation design. Additional subjects may be enrolled to have approximately 12 patients in each selected dose level for RDE determination. A randomized, open label, parallel-arm study will be conducted during the dose expansion part for further dose exploration. Approximately 40-60 subjects will be randomized in a 1:1 ratio into two treatment groups with dose levels selected from dose escalation part of the study. Randomization will be stratified based on disease type at enrollment (papillary-only vs. CIS). A dose selection analysis will be performed to assess safety, efficacy, PK, and PD, where applicable, to determine the optimal dose for RAG-01. The main study period includes the screening, initial treatment and DLT assessment period, second and third treatment period and the sequential follow-up period.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Ability to understand the study and have signed the informed consent form;
- •Any adult ≥ 18 years old;
- •Pathologically confirmed high grade NMIBC defined as grade 2 or grade 3 disease;
- •Expected survival ≥ 6 months;
- •ECOG PS ≤2;
- •Sufficient organ functions, as defined below:
- •Investigations Hematology Absolute Neutrophil Count (ANC): ≥ 1.5 x 109/L Hemoglobin: ≥ 90 g/L Platelet: ≥ 100 x 109/L Liver Function Serum bilirubin: ≤ 1.25×ULN or 2.5×ULN（with Gilbert syndrome） AST & ALT: ≤ 2.5×ULN Renal Function Creatinine Clearance (Cockcroft-Gault equation): ≥ 30 mL/min
- •Subject must be able to tolerate catheterization;
- •Female subject of childbearing potential and her spouse must use adopt effective contraception (non-pharmacological contraception required) from signing informed consent to within 6 months after the last instillation;
排除标准
- •Subject who is allergy to RAG-01 or similar products;
- •Except for TURBT, the subject received other anti-tumor treatments, and the last administration date is within ≤ 21 days or 5 half-lifes whichever is shorter from the date of signing ICF;
- •Subject with imaging examination diagnosed extravesical metastasis, including ureter and urethra;
- •Subject has other malignancies within the past 3 years, except for adequately treated carcinoma of the cervix, basal or squamous cell carcinomas of the skin, or adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is non-detectable;
- •The following illnesses have not been relieved to CTCAE 0-1:
- •Uncontrolled acute and chronic infections, such as pneumonia, biliary tract infection, hepatitis B virus infection and hepatitis C virus infection;
- •Acute and chronic kidney injury, and inflammation;
- •Urinary incontinence;
- •Urinary frequency;
- •Urinary tract obstruction (except benign prostatic hypertrophy);
- •Subject could not hold the urine for at least 90 mins due to any reason;
- •New York Heart Association (NYHA) 3 or 4 grade;
- •Coronary heart disease related symptoms have not been relieved to CTCAE 0-1, including: myocardial infarction, unstable angina pectoris, congestive heart failure and arrhythmia;
- •Subject with QTc >470 msec.
- •Cerebrovascular accidents have not been relieved to CTCAE 0-1;
- •HIV positive; Active hepatitis B or C. For active HBV, it's defined as HBsAg positive with HBV DNA ≥ ULN, for active HCV, it's defined as HCV antibody positive with HCV RNA ≥ ULN, respectively.
- •Subject is pregnant or lactating during the treatment period;
- •History of central nervous system or psychiatric disorders, e.g., epilepsy or dementia;
- •Other severe systemic diseases which might compromise the subject's compliance to the study, e.g., uncontrolled diabetes, gastrointestinal disorders, and renal diseases;
- •Any other situations which are judged by the investigator, would exposure the subject to unnecessary risk, therefore he/she is not eligible.
研究组 & 干预措施
RAG-01 dose escalation and dose expansion
The starting dose of RAG-01 is 30mg, and there are 4 dose cohorts, including 30mg, 100mg, 300mg, 600mg, respectively. Each eligible subject will be distributed into one cohort. Safety and pharmacokinetics are assessed at each dose level.
干预措施: RAG-01 (Drug)
结局指标
主要结局
Safety and tolerability of RAG-01 in patients with non-muscle-invasive bladder cancer (NMIBC)
时间窗: From the screening to 6 months after the first instillation of RAG-01
Adverse events (AEs), serious adverse events (SAEs), and adverse events during treatment (TEAEs)
Maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of RAG-01
时间窗: Within 21 days after first instillation
Dose-limiting toxicity (DLT)
次要结局
未报告次要终点