NCT03127215已完成2 期
A Randomized Phase-2 Study of Trabectedin/Olaparib Compared to Physician's Choice in Subjects With Previously Treated Advanced or Recurrent Solid Tumors Harboring DNA Repair Deficiencies
National Center for Tumor Diseases, Heidelberg9 个研究点 分布在 1 个国家目标入组 102 人开始时间: 2018年10月25日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 102
- 试验地点
- 9
- 主要终点
- Disease Control Rate
研究概览
简要总结
Evaluation of the efficacy of the combination of olaparib and trabectedin in adult patients with locally advanced/metastatic solid tumors that failed standard treatment and whose molecular sequencing tumor profiles show homologous recombination repair (HRR) defects. The primary objective is to show superior disease control rate in patients with HRR-deficient tumors treated with olaparib and trabectedin compared to treatment according to current guidelines (physician's choice). This trial aims to establish whether the PARP-dependency of HRR-deficient tumors across entities can be exploited for therapeutic benefit.
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
盲法说明
open label
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Progressive locally advanced or metastatic malignancy
- •Prior administration of standard treatment for primary and relapsed malignancy
- •Eastern Cooperative Oncology Group Performance Status ≤1
- •Patients with central venous access device in place (central venous catheter or porta-cath)
- •Age ≥18 and ≤70 years
- •Identification of defective DNA repair via HR
- •Adequate bone marrow, renal, and hepatic function
- •Hemoglobin ≥10 g/dl
- •Neutrophil count ≥1,500/mm3
- •Platelet count ≥100,000/µl
- •Bilirubin ≤1.5 x upper limit of normal (ULN)
- •ALT and AST ≤2.5 x ULN (≤5 x ULN in patients with hepatic tumor involvement)
- •Alkaline phosphatase ≤2.5 x ULN
- •PT-INR/PTT ≤1.5 x ULN
- •Albumin ≥25 g/l
- •Creatine kinase ≤2.5 x ULN
- •Serum creatinine 1.5 mg/dl or creatinine clearance 51 ml/min
排除标准
- •Hematological malignancies and primary brain tumors.
- •Concurrent treatment in another interventional clinical trial
- •Prior treatment with PARP Inhibitors
- •Patients with platinum-refractory disease, defined as progressive disease during or immediately after treatment with platinum based chemotherapy
- •Persistent toxicity (> Grade 2 according to CTCAE 5.0)
- •Dementia or significant impairment of cognitive state
- •History of HIV infection
- •Clinical signs of active infection (>Grade 2 according to CTCAE 4.03)
- •History of viral hepatitis (HBV or HCV)
- •Epilepsy requiring pharmacologic treatment
- •Pregnancy
- •Major surgical intervention 4 weeks prior to study inclusion
- •Known hypersensitivity to any of the study drugs
- •Hematologic malignancy
- •QTc time prolongation >500 ms or history of familial long-QT-syndrome
- •Heart failure NYHA III/IV
- •Severe obstructive or restrictive ventilation disorder
- •Concomitant use of known strong CYP3A Inhibitors
- •Concomitant use of known strong CYP3A inducers
研究组 & 干预措施
Arm C: Physician's choice
Other
Physician's choice
干预措施: Physician's choice (Drug)
Arm E: Olaparib / Trabectedin
Experimental
Olaparib / Trabectedin
干预措施: Trabectedin (Drug)
Arm E: Olaparib / Trabectedin
Experimental
Olaparib / Trabectedin
干预措施: Olaparib (Drug)
结局指标
主要结局
Disease Control Rate
时间窗: At week 16 (after 5 cycles of study medication)
Randomized, open-label, multicenter phase-II study comparing olaparib in combination with trabectedin versus physician's choice. Primary efficacy endpoint is the disease control rate after 5 cycles.
次要结局
- Overall survival(Time from first administration of the IMP to time death from any cause until end of study (2.5 years))
- Incidence of Treatment-Emergent Adverse Events(Time from first administration of the IMP to subjects end of trial (approximately month 6))
- Patient reported outcomes(Before the first (week 0), at the third (week 8), and after the fifth treatment cycle (week 16))
- Tumor response rate(At week 16 (after 5 cycles of study medication))
研究者
研究点 (9)
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