临床试验/NCT03528694

NCT03528694

进行中（未招募）

3 期

A Phase III Randomized, Open-Label, Multi-Center, Global Study of Durvalumab and Bacillus Calmette-Guerin (BCG) Administered as Combination Therapy Versus BCG Alone in High-Risk, BCG Naïve Non-Muscle Invasive Bladder Cancer Patients

AstraZeneca121 个研究点分布在 8 个国家目标入组 1,018 人2018年5月14日

适应症Non-muscle-invasive Bladder Cancer

干预措施Durvalumab (MEDI4736)Bacillus Calmette-Guerin (BCG)

概览

阶段: 3 期
干预措施: Durvalumab (MEDI4736)
疾病 / 适应症: Non-muscle-invasive Bladder Cancer
发起方: AstraZeneca
入组人数: 1018
试验地点: 121
主要终点: The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC
状态: 进行中（未招募）
最后更新: 18天前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is a randomized, open-label, multi-center, global, phase III study to determine the efficacy and safety of Durvalumab + BCG combination therapy in the treatment of patients with non-muscle-invasive bladder cancer

详细描述

Patients will be randomized in a 1:1:1 ratio to receive treatment with Durvalumab + BCG combination therapies, or Standard of Care (SoC) therapy.

注册库

clinicaltrials.gov

开始日期

2018年5月14日

结束日期

2028年10月3日

最后更新

18天前

研究类型

Interventional

研究设计

Parallel

性别

All

研究者

发起方

AstraZeneca

责任方

Sponsor

入排标准

入选标准

•For inclusion in the study, patients should fulfill the following criteria:
•Aged at least 18 years
•BCG-naïve (patients who have not received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry are eligible)
•Local histological confirmation (based on pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa. A high risk tumor is defined as one of the following
•High grade/ G3 tumor
•Multiple and recurrent and large (with diameter of largest tumor ≥3 cm) tumors (all conditions must be met in this point)
•Complete resection of all Ta/T1 papillary disease prior to randomization, with the TURBT removing high-risk NMIBC performed not more than 4 months before randomization in the study. Patients with residual CIS after TURBT are eligible
•No prior radiotherapy for bladder cancer
•No prior exposure to immune-mediated therapy of cancer including, but not limited to, other anti CTLA-4, anti-PD-1, anti-PD-L1, and anti-programmed cell death ligand 2 antibodies. Patients who have been treated with anticancer vaccines will be excluded

排除标准

•Patients should not enter the study if any of the following exclusion criteria are fulfilled:
•Evidence of muscle-invasive, locally advanced, metastatic, and/or extra vesical bladder cancer (ie, T2, T3, T4, and / or stage IV)
•Concurrent extravesical (ie, urethra, ureter, or renal pelvis), non-muscle-invasive transitional cell carcinoma of the urothelium
•Previous investigational product (IP) assignment in the present study
•Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for noncancer related conditions (eg, hormone replacement therapy) is acceptable. Chemotherapy for previous instances of NMIBC is acceptable.
•Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[eg, colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]). The following are exceptions to this criterion:
•Patients with vitiligo or alopecia
•Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
•Any chronic skin condition that does not require systemic therapy
•Patients without active disease in the last 5 years may be included but only after consultation with the Study Physician

研究组 & 干预措施

Durvalumab plus BCG (induction only)

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

干预措施: Durvalumab (MEDI4736)

Durvalumab plus BCG (induction + maintenance)

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

干预措施: Bacillus Calmette-Guerin (BCG)

Durvalumab plus BCG (induction only)

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

干预措施: Bacillus Calmette-Guerin (BCG)

BCG treatment (Standard of care therapy)

Bacillus Calmette-Guerrin (BCG) standard of care treatment

干预措施: Bacillus Calmette-Guerin (BCG)

Durvalumab plus BCG (induction + maintenance)

Durvalumab (MEDI4736) plus Bacillus Calmette-Guerrin (BCG) combination therapy

干预措施: Durvalumab (MEDI4736)

结局指标

主要结局

The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of Disease free survival (DFS) in patients with NMIBC

时间窗: Up to 4 years

Disease-free survival using Investigator disease assessments.

次要结局

The serum concentration of Durvalumab plus BCG combination therapies(Up to 4 years)
The immunogenicity of Durvalumab when used in combination with BCG treatment assessed by descriptive summary of presence of ADAs(Up to 4 years)
The efficacy of durvalumab + BCG combination therapy compared to SoC in terms of CRR for patients with CIS prior to study entry or at baseline cystoscopy(Up to 4 years)
Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the EORTC QLQ-C30 questionnaire(Up to 4 years)
The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of OS(Up to 7 years)
The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of DFS after 24 months of last subject's last dose of IP(Up to 4 years)
The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of OS(Up to 7 years)
The efficacy of Durvalumab + BCG combination therapies compared to each other in terms of time to muscle invasive bladder cancer and/or metastatic disease(Up to 7 years)
Patient-reported treatment tolerability using specific PRO CTCAE symptoms(Up to 4 years)
The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of OS(Up to 7 years)
The efficacy of Durvalumab + BCG (induction plus maintenance) therapy compare to SoC in terms of DFS after 24 months of last subject's last dose of IP(Up to 4 years)
The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease(Up to 7 years)
Disease-related symptoms and HRQoL in patients with NMIBC treated with Durvalumab + BCG combination therapies compared to SoC and compared to each other using the the EORTC QLQ NMIBC24 questionnaire(Up to 4 years)
The efficacy of Durvalumab + BCG (induction plus maintenance) combination therapy compared to SoC in terms of time to muscle invasive bladder cancer and/or metastatic disease(Up to 7 years)
The efficacy of Durvalumab + BCG (induction only) combination therapy compared to SoC in terms of DFS after 24 months of last subject's last dose of IP(Up to 4 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of DFS 24 months(Up to 4 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of time to development of upper tract urothelial carcinoma(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of OS5(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of any disease-free survival(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone in terms of Time to MIBC and/or Metastatic Disease(Up to 4 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to BCG (induction and maintenance) alone with respect to time to cystectomy(Up to 4 years)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of Disease-free survival(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of patients alive and disease free at 24 months(Up to 24 months)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of OS5(up to 5 years)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of any disease-free survival(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of Time to MIBC and/or metastatic disease(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone in terms of time to cystectomy(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction only) combination therapy compared to BCG (induction and maintenance) alone time to development of upper tract urothelial carcinoma(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Disease-free survival(Up to 4 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Proportion of patients alive and disease free at 24 months(Up to 24 months)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Overall survival at 5 years(Up to 7 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of any disease-free survival(up to 5 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of time to MIBC and/or metastatic disease(up to 5 yeas)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of time to cystectomy(up to 5 years)
To assess the efficacy of durvalumab + BCG (induction and maintenance) combination therapy compared to durvalumab + BCG (induction only) in terms of Time to development of upper tract urothelial carcinoma(up to 5 years)
Complete response rate (CRR) at 6 months using Investigator disease assessments(up to 6 months)
EORTC QLQ-C30 and EORTC QLQ-NMIBC24(up to 5 years)
PRO version of the CTCAE with approximately 19 items (PRO-CTCAE) symptoms in countries where language is available(up to 5 years)
PK serum concentration of durvalumab(up to 5 years)
Presence of ADAs for durvalumab(up to 5 years)