A Phase III, Randomized, Open-Label, Controlled, Multi-Center, Global Study of First-Line Durvalumab in Combination With Standard of Care Chemotherapy and Durvalumab in Combination With Tremelimumab and Standard of Care Chemotherapy Versus Standard of Care Chemotherapy Alone in Patients With Unresectable Locally Advanced or Metastatic Urothelial Cancer.
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 1,246
- 试验地点
- 223
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This is a randomized, open-label, controlled, multi-center, global Phase III study to determine the efficacy and safety of combining durvalumab ± tremelimumab with standard of care (SoC) chemotherapy (cisplatin + gemcitabine or carboplatin + gemcitabine doublet) followed by durvalumab monotherapy versus SoC alone as first-line chemotherapy in patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra).
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
- •Patients with histologically or cytologically documented, unresectable, locally advanced or metastatic transitional cell carcinoma (transitional cell and mixed transitional/non-transitional cell histologies) of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra)
- •Patients who have not been previously treated with first-line chemotherapy. Patients who have received prior definitive chemoradiation, adjuvant or neoadjuvant treatment for locally advanced disease are eligible provided that progression to locally advanced or metastatic disease has occurred >12 months from the last therapy [for chemoradiation and adjuvant treatment] or >12 months from the last surgery [for neoadjuvant treatment].
- •At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 target lesion at baseline.
- •World Health Organization (WHO)/Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 at enrolment
- •Adequate organ and marrow function as defined in the protocol
- •Life expectancy ≥12 weeks in the opinion of the investigator
- •Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
排除标准
- •Prior exposure to immune-mediated therapy (with exclusion of Bacillus Calmette Guerin), including but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD L1, or anti-PD-L2 antibodies, except therapeutic anticancer vaccines, which are permitted. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
- •No severe concomitant condition that requires immunosuppression medication
- •Untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
- •Patients who may be eligible for or are being considered for radical resection during the course of the study.
- •Any medical contraindications to platinum (cisplatin or carboplatin) based doublet chemotherapy and/or known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
研究组 & 干预措施
Durvalumab in Combination with SoC Chemotherapy
Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Durvalumab (Drug)
Durvalumab in Combination with Tremelimumab+SoC Chemotherapy
Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks
Tremelimumab will be provided for 4 cycles.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Tremelimumab (Drug)
SoC Chemotherapy
Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Cisplatin + Gemcitabine (Drug)
Durvalumab in Combination with SoC Chemotherapy
Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Carboplatin + Gemcitabine (Drug)
Durvalumab in Combination with Tremelimumab+SoC Chemotherapy
Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks
Tremelimumab will be provided for 4 cycles.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Cisplatin + Gemcitabine (Drug)
Durvalumab in Combination with SoC Chemotherapy
Durvalumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Cisplatin + Gemcitabine (Drug)
SoC Chemotherapy
Patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Carboplatin + Gemcitabine (Drug)
Durvalumab in Combination with Tremelimumab+SoC Chemotherapy
Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks
Tremelimumab will be provided for 4 cycles.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Carboplatin + Gemcitabine (Drug)
Durvalumab in Combination with Tremelimumab+SoC Chemotherapy
Durvalumab and Tremelimumab every 3 weeks in concurrence with chemotherapy, followed by durvalumab monotherapy every 4 weeks
Tremelimumab will be provided for 4 cycles.
All patients will receive one of the following standard of care chemotherapy regimens every 3 weeks for 6 cycles:
- cisplatin+ gemcitabine
- If the patient is cisplatin-ineligible, carboplatin + gemcitabine
干预措施: Durvalumab (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: approximately 5 years
OS is defined as the time from the date of randomization until death due to any cause
次要结局
- Overall Survival (OS)(approximately 5 years)
- Overall Survival at 24 months (OS24)(24 months)
- Progression Free Survival (PFS)(approximately 5 years)
- Alive and Progression Free Survival at 12 months (APF12)(12 months)
- Objective Response Rate (ORR)(approximately 5 years)
- Duration of Response (DoR)(approximately 5 years)
- Disease Control Rate (DCR)(approximately 5 years)
- Time from randomization to second (PFS2)(approximately 5 years)
- To assess disease-related symptoms, physical functioning, and other Health-related quality of life(approximately 5 years)