A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer
概览
- 阶段
- 2 期
- 干预措施
- Durvalumab
- 疾病 / 适应症
- Urinary Bladder Neoplasms
- 发起方
- AstraZeneca
- 入组人数
- 154
- 试验地点
- 44
- 主要终点
- Progression-free Survival (PFS)
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
A Phase II, Randomized, Multi-Center, Double-Blind, Comparative Global Study to Determine the Efficacy and Safety of Durvalumab in Combination With Olaparib for First-Line Treatment in Platinum-Ineligible Patients With Unresectable Stage IV Urothelial Cancer
详细描述
This is a Phase II, randomized, double-blind, placebo controlled, multi-center, comparative global study to determine the efficacy and safety of durvalumab + olaparib combination therapy versus durvalumab + placebo (durvalumab monotherapy) as first-line treatment in patients ineligible for platinum-based chemotherapy with unresectable Stage IV urothelial cancer (UC).
研究者
入排标准
入选标准
- •Provision of signed and dated, written ICF
- •Histologically or cytologically documented TCC/UC of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) also meeting the following: Unresectable, Stage IV disease; No prior systemic therapy for unresectable, Stage IV disease.
- •Ineligible for platinum-based chemotherapy defined as (i) in the opinion of the Investigator, unfit for carboplatin-based chemotherapy and (ii) meeting one of the following criteria: CrCl \<60 mL/min calculated by Cockcroft-Gault equation; Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss (25 dB in 2 consecutive wave ranges); CTCAE Grade ≥2 peripheral neuropathy; New York Heart Association Class III heart failure; ECOG
- •Known tumor HRR mutation status prior to randomization.
- •World Health Organization (WHO)/ECOG performance status of 0, 1, or
- •Patients with at least 1 RECIST 1.1 target lesion at baseline.
- •Ability to swallow oral medications.
- •Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
排除标准
- •Active or prior documented autoimmune or inflammatory disorders.
- •Other invasive malignancy within 5 years before the first dose of the IP.
- •Major surgical procedure within 28 days prior to the first dose
- •Brain metastases or spinal cord compression unless the patient's condition is stable and off steroid for at least 14 days
- •History of active primary immunodeficiency.
- •Active infection including tuberculosis (TB)
- •History of allogenic organ transplantation.
- •Uncontrolled intercurrent illness
- •Prior exposure to a PARP inhibitor or immune-mediated therapy.
- •Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
研究组 & 干预措施
Arm 1: Durvalumab/Placebo
Durvalumab 1500 mg intravenous (IV) every 4 weeks (q4w) starting on week 1 day 1/Placebo orally (PO) twice a day (BID) starting on week 1 day 1.
干预措施: Durvalumab
Arm 1: Durvalumab/Placebo
Durvalumab 1500 mg intravenous (IV) every 4 weeks (q4w) starting on week 1 day 1/Placebo orally (PO) twice a day (BID) starting on week 1 day 1.
干预措施: Placebo
Arm 2: Durvalumab/Olaparib
Durvalumab 1500 mg IV q4w starting on week 1 day 1/Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.
干预措施: Durvalumab
Arm 2: Durvalumab/Olaparib
Durvalumab 1500 mg IV q4w starting on week 1 day 1/Olaparib PO 300 mg BID adjusted based on patient's creatinine clearance.
干预措施: Olaparib
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: Assessments performed at baseline and every 8 weeks from date of randomization until date of objective disease progression or death (by any cause in the absence of progression), assessed up to the data cut-off date (15 Oct 2020), up to a max. of 31 months
Progression-free survival based on investigator assessments according to RECIST 1.1
次要结局
- Duration of Response (DoR)(Tumor assessments every 8 weeks after randomization for the first 48 weeks and then every 12 weeks thereafter until the date of objective disease progression. Assessed up to the data cut-off date (15 October 2020), to a maximum of 31 months)
- Overall Survival (OS)(From the date of randomization until the death due to any cause, assessed up to the data cut-off date (15 October 2020), to a maximum of 31 months)
- Objective Response Rate (ORR)(From the date of randomization to the date of progression or the last evaluable assessment in the absence of progression, assessed up to the data cut-off date (15 October 2020), to a maximum of 31 months)