A Phase IIIb Open-Label, Single-Arm, Multi-Center, US Study of Bacillus Calmette-Guerin (BCG) Administered in Combination With Durvalumab in Adult BCG-naïve, High-risk Non-Muscle- Invasive Bladder Cancer Participants (PATAPSCO)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 100
- 试验地点
- 20
- 主要终点
- Incidence of Grade 3 or 4 Possibly related adverse events (PRAEs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, and efficacy profile of durvalumab + BCG (induction and maintenance) combination therapy in adult United States participants with a histologically confirmed diagnosis of high-risk non-muscle-invasive bladder cancer (NMIBC), who have received no prior systemic therapy for NMIBC, and who are BCG-naïve.
详细描述
This is an open-label, single-arm, multi-center, Phase IIIb US study exploring the combination of durvalumab and BCG (induction and maintenance) in participants with high-risk NMIBC.
Each participant will have screening activities up to 4 weeks before initiation of study intervention, receive study intervention for up to 24 months, followed by 3 months safety follow-up. Participants will continue to be followed up for survival until 2 years from the date of treatment initiation of the last participant enrolled in this study (approximately 42 months after first participant enrolled).
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 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BCG-naïve (defined as participants not having received prior intravesical BCG or who previously received but stopped BCG more than 3 years before study entry).
- •Local histological confirmation (based on cytology and/or pathology report) of high-risk transitional cell carcinoma of the urothelium of the urinary bladder confined to the mucosa or submucosa.
- •Complete resection of all Ta/T1 papillary disease prior to enrollment, with the transurethral resection of bladder tumor (TURBT) removing high-risk NMIBC (non-muscle invasive bladder cancer) performed not more than 4 months before enrollment in the study.
- •No prior radiotherapy for bladder cancer.
- •A life expectancy of at least 12 weeks (90 days).
- •Adequate organ and marrow function
- •World Health Organization/Eastern Cooperative Oncology Group performance status of 0 or 1 at screening
- •No prior exposure to immune-mediated therapy of cancer
- •A candidate for BCG treatment.
- •Local histological confirmation (based on cytology and/or 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: T1 tumor; High-grade/G3 tumor; CIS.
排除标准
- •Evidence of muscle-invasive, locally advanced, metastatic, and/or extra-vesical bladder cancer (ie, T2, T3, T4, and / or Stage IV).
- •Predominantly variant histology such as micropapillary, plasmacytoid, nested, sarcomatoid, microcystic, squamous and adeno variants of UC representing > 50% of tumor tissue or other than urothelial tumors as assessed by pathology.
- •Evidence of lymphovascular invasion of bladder tumor, except if treatment with BCG is deemed to be the only clinically viable treatment.
- •Immediate cystectomy is indicated.
- •Known or documented absolute and/or relative contraindication of adjuvant intravesical BCG treatment.
- •Concurrent extravesical, non-muscle-invasive transitional cell carcinoma of the urothelium.
- •History of allogenic organ transplantation. Participants with any history of allogenic stem cell transplantation are also excluded.
- •Active or prior documented autoimmune or inflammatory disorders.
- •Participants with hypothyroidism stable on hormone replacement.
- •History of active primary immunodeficiency.
- •Active infection including hepatitis B (known positive HBV/HBsAg result), HCV, or HIV 1/2 (positive HIV) antibodies.
- •Current or prior use of immunosuppressive medication within 14 days before the first durvalumab dose.
- •Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ highly effective birth control.
- •Any concurrent chemotherapy, study intervention, biologic or hormonal therapy for cancer treatment; uncontrolled intercurrent illness;
- •History of another primary malignancy except for Malignancy treated with curative intent and with no known active disease ≥ 2 years; Adequately treated nonmelanoma skin cancer or lentigo maligna without evidence of disease; Adequately treated CIS without evidence of disease; Prostate cancer of stage ≤ T2cN0M0 without biochemical recurrence or progression that in the opinion of the Investigator does not require active intervention.
- •Previous or concurrent treatment with potent systemic immunostimulatory agents
研究组 & 干预措施
Durvalumab + BCG
Participants will receive Durvalumab for 13 cycles every 4 weeks (q4w) for a maximum 12 months. All participants will receive BCG (supplied by the site) intravesically, as induction weekly for 6 weeks. Patients will subsequently receive BCG for maintenance for 3 weekly doses at 3,6,12,18, and up to 24 months, at the physician's discretion.
干预措施: Durvalumab (Biological)
Durvalumab + BCG
Participants will receive Durvalumab for 13 cycles every 4 weeks (q4w) for a maximum 12 months. All participants will receive BCG (supplied by the site) intravesically, as induction weekly for 6 weeks. Patients will subsequently receive BCG for maintenance for 3 weekly doses at 3,6,12,18, and up to 24 months, at the physician's discretion.
干预措施: BCG (Biological)
结局指标
主要结局
Incidence of Grade 3 or 4 Possibly related adverse events (PRAEs)
时间窗: From the date of the first dose of study treatment (Day 1) until 6 months after the initiation of study treatment
A PRAE is defined as an AE that has been assessed by the Investigator to be possibly related to study treatment. A PRAE will be included if it has onset or worsens (by Investigator report of an increase in CTCAE (common terminology criteria for adverse events) grade relative to pre-treatment) within 6 months of initiation of study intervention and it has CTCAE Grade 3 or 4 recorded within this timeframe.
次要结局
- Number of participants with adverse events (AEs)(From screening (Day -28 to -1) until 90 days following discontinuation of the last dose of study treatment (approximately 28 months))
- Complete response rate (CRR)(At 6 months)
- Disease-free survival (DFS)(At 12 months and 24 months)
- Percentage of patient-reported treatment tolerability symptoms assessed using specific PRO-CTCAE (Patient-Reported Outcomes- Common Terminology Criteria for Adverse Events)(Up to 24 months)
- Overall survival (OS)(At 24 months)
- Best overall response for HRQoL as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Non-Muscle-Invasive Bladder Cancer 24 (EORTC QLQ-NMIBC24)(Up to 24 months)
- Best overall response for health-related quality of life (HRQoL) as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 items (EORTC QLQ-C30)(Up to 24 months)