A Randomized, Double-Blind, Placebo-Controlled Phase I Trial to Evaluate the Immunomodulatory Effect of RUTI® in Individuals With High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) Treated With Intravesical Bacillus Calmette-Guerin (BCG)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Changes in the systemic Th1 immune response.
研究概览
简要总结
The RUTIVAC-1 study is a Phase I Clinical Trial designed to evaluate the systemic and mucosal immunological response and provide safety information after the use of RUTI® administration to individuals with NMIBC.
The study will enroll individuals treated with Transurethral resection of bladder tumor (TURBT), diagnosed to have high-risk Non-muscle invasive bladder cancer (NMIBC) and suitable candidates for BCG therapy and who meet all eligibility criteria.
Forty individuals will be recruited and randomized 1:1 to receive two subcutaneous shots of 25 μg RUTI® or placebo. After vaccination, individuals will receive the standard induction course, of intravesical Bacillus Calmette-Guerin (BCG)therapy (weekly BCG for six weeks).
4 to 8 weeks after the last intravesical BCG administration (BCG6) a visit will be performed (Visit 1, end of the interventional phase). Once all participants have performed VISIT 1 immunological assays will be performed and data will be analyzed.
At the end of the Interventional Phase the blind will be opened, except for the study physicians who will remain blind during all the follow-up. All the individuals will be followed up for three years since TURBT.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written ICF for participation in the study.
- •Age ≥18 years.
- •General health status according to WHO ≤
- •Have primary histologically confirmed T1 and/or high grade tumors and/or CIS.
- •All visible papillary tumors must be completely resected.
- •Early postoperative (within 24 hours of TURBT) single dose chemotherapy is allowed.
- •BCG therapy indication.
- •Never treated with BCG immunotherapy
- •Willing to comply with study visits and procedures as per protocol
- •Use of reliable contraception (see section 8.6) from the screening visit to 30 days after the last RUTI® or placebo injection.
排除标准
- •Life expectancy <5 years.
- •Have a severe concomitant disease that might limit compliance or completion of the protocol.
- •Have any other malignancy that might impact 3-year survival or might be potentially confused with NMIBC.
- •Have other neoplasms.
- •Have congenital or acquired immune deficiencies or under immunomodulatory treatment.
- •Be receiving cytotoxic drugs or systemic corticosteroids within 8 weeks of receiving the first administration of BCG.
- •Have received radiation therapy for their bladder cancer within 4 months prior to study entry.
- •Have active infections (including urinary tract infections) defined as viral, bacterial, or fungal infections requiring therapy, HIV-positive status, concurrent febrile illness, gross hematuria or other factor that could influence tolerability to intravesical BCG therapy.
- •Have biopsy, TURBT, or traumatic catheterization within 14 days of start of intravesical BCG treatment.
- •Have active tuberculosis at screening visit.
- •Active pregnancy or breastfeeding.
- •Soy allergy
研究组 & 干预措施
RUTI® injection
干预措施: RUTI® (Drug)
Sodium Chloride 0.9% injection
干预措施: Placebo (Drug)
结局指标
主要结局
Changes in the systemic Th1 immune response.
时间窗: Baseline, Day 10, weeks 2, 7 and 16
IFN-γ production assessed by intracellular staining after ex vivo stimulation of PBMCs with PPD
Changes in the local immune response in urine
时间窗: Baseline, Day 10, weeks 2, 7 and 16
Urine levels of cytokines by multiplex analysis
Changes in the local immune response in peritumoral tissue (Th1/Th2 ratio)
时间窗: Baseline and week 16 visit
Th1/Th2 ratio in cells in the peritumoral tissue
次要结局
- Proportion of patients who develop a Grade 3 or 4 systemic reactions(through study completion an average of 1,5 year)
- Disease worsening(Until 3 years since TURBT)
- Recurrence date(Until 3 years since TURBT)
- Death(Until 3 years since TURBT)
- Proportion of patients who develop a Grade 3 or 4 local reactions(through study completion an average of 1,5 year)