NCT03579628已完成1 期
An Open-label, Dose-escalation Phase I/Ib Study to Assess the Safety, Pharmacokinetics and Pharmacodynamics of AsiDNA, a DNA Repair Inhibitor Administered Intravenously, as Single Agent and to Assess the Safety and the Efficacy of AsiDNA in Combination With Carboplatin With or Without Paclitaxel, in Patients With Advanced Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 33
- 试验地点
- 5
- 主要终点
- Determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of iv infusions of AsiDNA.
研究概览
简要总结
The aim of the study is to assess:
- Part A: the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of AsiDNA in patients with advanced solid tumors.
- Part B: the safety and preliminary efficacy of AsiDNA in combination with Carboplatin with or without Paclitaxel in patients with Advanced solid tumors.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy of at least 3 months.
- •Patient with histologically or cytologically documented advanced/metastatic primary or recurrent solid tumors who failed or are not eligible to standard therapy (Part A) and who are candidate to Carboplatin (Part B1) and to Carboplatin and Paclitaxel (Part B2).
- •Part A: Fresh tumor sample from a biopsy
- •Part B: A most recent available tumor sample from a biopsy for all patients will be collected for retrospective analysis of 6 genes expression profile for validation of further stratification approach (exploratory purpose).
- •Prior anticancer therapies (chemotherapy, radiation therapy, hormonal therapy, immunotherapy, biological therapy) are allowed under conditions
- •At least one measurable lesion according to RECIST 1.1; Patient with no measurable lesion can be enrolled, if the tumor evaluation can be properly documented
- •Must meet select hematological and biochemical laboratory indices
- •Part B only:
- •Patient must be eligible to Carboplatin (Part B1) and to Carboplatin + weekly Paclitaxel (Part B2).
- •Patients must not have received more than 6 prior cycles of platinum-based chemotherapy.
排除标准
- •Patient with symptomatic/active central nervous system (CNS) metastases
- •Other tumor location necessitating an urgent therapeutic intervention
- •Patient with uncontrolled disease-related metabolic disorder
- •Patient presenting the following abnormal laboratory values at screening:
- •hematuria > 1+ on dipstick,
- •proteinuria > 1+ on dipstick
- •Patient with uncontrolled congestive heart failure defined as New York Heart Association (NYHA) class III or IV, uncontrolled hypertension, unstable heart disease
- •Patient with significant ECG abnormalities defined as any cardiac dysrhythmia (> grade 2)
- •Patient with significant chronic liver disease or active HBV or HCV infection
- •Patients with HIV infection or an active infection requiring specific anti-infective therapy
- •Participation in another clinical trial with any investigational drug within 28 days prior to first study drug administration.
研究组 & 干预措施
AsiDNA
Experimental
Part A: AsiDNA as a single agent:
The study will follow a dose escalation "3 + 3" cohort design (with 6 dose levels).
All patients will receive a loading dose of AsiDNA for 3 consecutive days as iv infusion at Day 1 (D1), Day 2 (D2) and Day 3 (D3), followed by iv infusion once a week (at D8 and D15 of a 21 days treatment period (1 cycle = 21 days). Each subsequent cycle will be administered on a weekly basis (D1, D8, D15) of a 21 days treatment period.
Part B: AsiDNA combination with Carboplatin with or without Paclitaxel (Background treatments):
- Part B1: Combination cohort of AsiDNA at DL3 (600mg) with Carboplatin AUC 5.
- Part B2: Combination cohort of AsiDNA at DL3 (600mg) with Carboplatin AUC 5 and weekly Paclitaxel: 80 mg/m2 (full dose).
干预措施: AsiDNA (Drug)
结局指标
主要结局
Determine dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of iv infusions of AsiDNA.
时间窗: At Cycle 1 (a cycle is 21 days for Part A and 28 days for Part B) for all patients
DLTs will be based on the toxicities observed during the first 3 weeks of study treatment (i.e, cycle 1: from Day 1 to Day 21) for Part A and during the 4 weeks of study treatment (i.e, cycle 1: from Day 1 to Day 28) for Part B. MTD is defined as the dose immediately below the unacceptable dose or defined as the highest tested dose if no DLT observed at this dose.
次要结局
- Collection of new Adverse Events and follow-up of all ongoing Adverse Events assessed(At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at Cycle 2 (at Day 1; Day 8; Day 15) and at each subsequent cycles in any (at Day 1; Day 8; Day 15) for all patients)
- Elimination half-life (t1/2) of iv infusions of AsiDNA(At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients)
- ECG evaluation for safety assessment(Before each cycle (e.g at Day 1 of cycle 1; Day 1 of cycle 2 and Day 1 of each subsequent cycles if any) per usual center's practice.)
- Peak plasma concentration of iv infusions of AsiDNA(At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients)
- Time to peak plasma concentration of iv infusions of AsiDNA(At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients)
- Area under the curve of iv infusions of AsiDNA(At Cycle 1 (at Day 1; Day 3; Day 8; Day 15) and at cycle 2 (at Day 1) for all patients)
- Accumulation factor based on total plasma exposure of iv infusions of AsiDNA(At Cycle 1 (at Day 1) and at cycle 2 (at Day 1) for all patients)
研究者
研究点 (5)
Loading locations...
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