NCT03732677进行中（未招募）3 期
A Phase III, Randomized, Open-Label, Multi-Center, Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Gemcitabine+Cisplatin for Neoadjuvant Treatment Followed by Durvalumab Alone for Adjuvant Treatment in Patients With Muscle-Invasive Bladder Cancer.
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,063
- 试验地点
- 188
- 主要终点
- Pathologic Complete Response (pCR) Rates at Time of Cystectomy
研究概览
简要总结
A Global Study to Determine the Efficacy and Safety of Durvalumab in Combination with Gemcitabine+Cisplatin for Neoadjuvant Treatment and Durvalumab Alone for Adjuvant Treatment in Patients with Muscle-Invasive Bladder Cancer
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
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient resectable muscle-invasive bladder cancer with clinical stage T2-T4aN0/1M0 with transitional and mixed transitional cell histology
- •Patients must be planning to undergo a radical cystectomy
- •Patients who have not received prior systemic chemotherapy or immunotherapy for treatment of MIBC
- •ECOG performance status of 0 or 1
- •Must have a life expectancy of at least 12 weeks at randomization
排除标准
- •Evidence of lymph node (N2-N3) or metastatic (M1) disease at time of screening.
- •Prior pelvic radiotherapy treatment within 2 years of randomization to study
- •Prior exposure to immune-mediated therapy (with exclusion of Bacillus-Calmette Guerin [BCG]), including but not limited to other anti-CTLA-4, anti-PD-1, anti PD-L1, or anti-PD-L2 antibodies.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection); Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent; Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
- •Uncontrolled intercurrent illness
- •Active infection including Tuberculosis, Hepatitis B, Hepatitis C, and Human Immunodeficiency
研究组 & 干预措施
Arm 2
Active Comparator
Chemotherapy alone
干预措施: Cisplatin (Drug)
Arm 1
Experimental
Chemotherapy + Durvalumab
干预措施: Cisplatin (Drug)
Arm 1
Experimental
Chemotherapy + Durvalumab
干预措施: Gemcitabine (Drug)
Arm 1
Experimental
Chemotherapy + Durvalumab
干预措施: Durvalumab (Drug)
Arm 2
Active Comparator
Chemotherapy alone
干预措施: Gemcitabine (Drug)
结局指标
主要结局
Pathologic Complete Response (pCR) Rates at Time of Cystectomy
时间窗: Up to 6 months
pCR rate is defined as the proportion of patients whose pathological staging was T0N0M0 as assessed per central pathology review using specimens obtained via radical cystectomy following the neoadjuvant treatment. The denominator for pCR will be the number of patients in the FAS.
Event-free Survival (EFS) Per Central Review Defined as Time From Randomization to Event
时间窗: Up to 48 months
EFS is defined as the time from randomization to the first recurrence of disease post radical cystectomy, time of first documented progression in patients who were medically precluded for radical cystectomy, or time of expected surgery in patients who refuse to undergo a radical cystectomy or failure to undergo a radical cystectomy in participants with residual disease, or the time of death due to any cause, whichever occurs first
次要结局
- Proportion of Patients Who Undergo Cystectomy(Up to 6 months)
- Overall Survival(Up to 65 months)
- Metastasis-free Survival Per Investigator Assessment or Local Biopsy Review.(Up to 48 months)
- Disease-specific Survival Per Investigator Assessment or Local Biopsy Review.(Up to 48 months)
- Event-free Survival at 24 Months (EFS24) Per Central Review Defined as Time From Randomization to Event(Up to 24 months)
- Immunogenicity of Durvalumab When Used in Combination With Gemcitabine/Cisplatin as Measured by Presence of Antidrug Antibodies (ADA)(Up to 12 months)
研究者
研究点 (188)
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相关资讯
Durvalumab Gains Priority Review for Muscle-Invasive Bladder Cancer Treatment- The FDA has granted priority review to durvalumab (Imfinzi) for muscle-invasive bladder cancer (MIBC), potentially expediting its approval.
- Phase 3 NIAGARA trial data supports the application, showing a 32% reduction in disease progression or recurrence with perioperative durvalumab.
- The Imfinzi regimen also demonstrated a 25% reduction in the risk of death, offering a significant survival benefit.
- Regulatory decisions are anticipated in the second quarter of 2025, with potential implications for MIBC treatment standards.last yearDurvalumab Demonstrates Improved Survival in Liver and Bladder Cancers- Durvalumab plus tremelimumab showed a 24% reduction in death risk versus sorafenib in unresectable hepatocellular carcinoma (HCC), with 19.6% alive at 5 years versus 9.4%.
- In muscle-invasive bladder cancer (MIBC), durvalumab with chemotherapy reduced disease progression, recurrence, or death by 32% compared to chemotherapy alone.
- Durvalumab-based regimens also improved overall survival in MIBC, reducing the risk of death by 25% compared to neoadjuvant chemotherapy and radical cystectomy.last yearPerioperative Durvalumab Plus Chemotherapy Improves Survival in Muscle-Invasive Bladder Cancer- Perioperative durvalumab combined with neoadjuvant chemotherapy significantly improved event-free survival (EFS) compared to chemotherapy alone in cisplatin-eligible MIBC patients.
- The durvalumab regimen also demonstrated a 25% reduction in the risk of death, showing a statistically significant overall survival (OS) benefit.
- A re-analysis of pathologic complete response (pCR) rates showed nominal statistical significance favoring the durvalumab arm, supporting the perioperative approach.
- The addition of perioperative durvalumab to neoadjuvant chemotherapy was tolerable, with no new safety signals observed in the NIAGARA trial.2 years agoDurvalumab Plus Chemotherapy Improves Outcomes in Muscle-Invasive Bladder Cancer- The NIAGARA phase 3 trial demonstrated that perioperative durvalumab combined with neoadjuvant chemotherapy significantly improved event-free survival in cisplatin-eligible MIBC patients.
- Overall survival was also significantly improved with the addition of durvalumab, showing a 25% reduction in the risk of death compared to chemotherapy alone.
- The combination of durvalumab and chemotherapy did not result in a significant increase in grade 3 or 4 adverse events compared to chemotherapy alone, suggesting a manageable safety profile.
- These findings support perioperative durvalumab with neoadjuvant chemotherapy as a potential new standard of care for cisplatin-eligible muscle-invasive bladder cancer.2 years ago