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
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 154
- 试验地点
- 45
- 主要终点
- Progression-free Survival (PFS)
研究概览
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •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.
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of the IP.
- •No radiation therapy is allowed, unless it is (1) definitive radiation that had been administered at least 12 months prior; (2) palliative radiation to the brain, with associated criteria for stability or lack of symptoms; or (3) palliative radiation to painful bony lesions (this must comprise less than 30% of the bone marrow) or symptomatic pelvic soft tissue mass(es).
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of the IP.
- •Patients with a known hypersensitivity to durvalumab, olaparib, or any of the excipients of the products.
- •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 6 months for participants taking also Olaparib in case of female participants, 90 days after receipt of the last dose of the IP in case of male participants.
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: Placebo (Drug)
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 (Drug)
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 (Drug)
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 (Drug)
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)