NCT02601378终止1 期
A Phase I, Multi-center, Open-label, Study of LXS196, an Oral Protein Kinase C Inhibitor, in Patients With Metastatic Uveal Melanoma
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 107
- 试验地点
- 2
- 主要终点
- Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
研究概览
简要总结
This study was to characterize the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of LXS196 as a single agent and in combination with HDM201 in patients with metastatic uveal melanoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •Male or female patients ≥18 years of age
- •Diagnosis of uveal melanoma with histological or cytological confirmed metastatic disease. Disease must be treatment naive or have progressed (radiologically or clinically) on most recent therapy.
- •Willingness to provide newly obtained tumor tissue at baseline and on treatment unless contraindicated by medical risk in the opinion of the treating physician.
- •Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as >10 mm with CT scan.
- •ECOG performance status ≤ 1
排除标准
- •Malignant disease other than that being treated in this study.
- •Symptomatic or untreated CNS metastases or spinal cord compression. Brain metastasis must be stable with verification by imaging .
- •Impaired cardiac function or clinically significant cardiac diseases
- •History of thromboembolic or cerebrovascular events within the last 6 months, including transient ischemic attack, cerebrovascular accident, deep vein thrombosis, or pulmonary embolism (applicable to combination part only).
- •Patients who are receiving treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following:
- •known and possible risk for QT prolongation
- •known to be strong inducers or inhibitors of CYP3A4/5 (for single agent part); known to be moderate to strong inducers or inhibitors of CYP3A4/5 (for combination part)
- •known to be inducers or inhibitors of P-gp
- •known to be substrates of CYP3A4/5 and P-gp with a narrow therapeutic index
- •Patients with abnormal laboratory values, defined as any of the following:
- •AST or ALT > 3 times ULN, AST or ALT > 5 times ULN for patients with liver metastases.
- •Total bilirubin > 1.5 x ULN, except for patients with Gilbert's syndrome who are excluded if total bilirubin > 3.0 x ULN or direct bilirubin > 1.5 x ULN.
- •Absolute neutrophil count (ANC) ≤ 1.5 x109/L.
- •Platelets ≤ 100 x 109/L.
- •Hemoglobin (Hgb) ≤ 90 g/L (9 g/dL).
- •Creatinine > 1.5 x ULN
- •Patients receiving live vaccines due to the expected bone marrow toxicity (applicable to combination part only).
- •Patients treated with growth factors targeting the myeloid lineage (e.g. G-CSF, GM-CSF and M-CSF) within 2 weeks of starting study treatment. (applicable to combination part only).
研究组 & 干预措施
LXS196 as a single agent
Experimental
About 68 patients will be enrolled in dose escalation and expansion
干预措施: LXS196 (Drug)
LXS196 in combination with HDM201
Experimental
about 44 patients to be enrolled in dose escalation and expansion
干预措施: LXS196 and HDM201 (Drug)
结局指标
主要结局
Incidence of dose limiting toxicities (DLTs) (Dose escalation only)
时间窗: Cycle 1 in dose escalation
cycle = 28 days
Incidence and severity of adverse events and serious adverse events, including changes in laboratory parameters, vital signs and ECGs graded as per NCI CTCAE version 4.03 (All patients)
时间窗: Continuously throughout the study until 30 days after treatment discontinuation
Dose interruptions, reductions and dose intensity
时间窗: Continuously throughout the study until 30 days after treatment discontinuation
次要结局
- Plasma PK parameters of LXS196 in combination with HDM201: Racc(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1)
- Overall response rate (ORR) per RECIST version 1.1 criteria(From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months)
- Plasma LXS196 concentration-time profiles as a single agent(Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1)
- Progression free survival (PFS) per RECIST version 1.1 criteria(From baseline, every 2 cycles until cycle 11, then every 3 cycles afterwards until disease progression or withdrawal of consent up to 12 months)
- Plasma PK parameters of LXS196 as a single agent:AUC(Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 as a single agent: Cmax(Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 as a single agent: Tmax(Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1)
- LXS196 plasma protein binding as a single agent(Cycle 1 Day 1, 2, 15, 16)
- LXS196 plasma protein content as a single agent(Cycle 1, 2, 3 and 4 Day 1)
- Modulation of signaling molecules downstream of PKC(Baseline and Cycle 1 Day 15)
- Plasma PK parameters of LXS196 as a single agent: t1/2(Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 as a single agent: Racc(Cycle 1 Day 1, 2, 3, 15; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma HDM201 concentration-time profiles(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1)
- Plasma PK parameters of HDM201: AUC(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1)
- Plasma PK parameters of HDM201: Cmax(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1)
- Plasma PK parameters of HDM201: Tmax(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1)
- Plasma PK parameters of HDM201: t1/2(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day 1)
- Plasma LXS196 concentration-time profiles in combination with HDM201(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 in combination with HDM201:AUC(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 in combination with HDM201: Cmax(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 in combination with HDM201: Tmax(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1)
- Plasma PK parameters of LXS196 in combination with HDM201: t1/2(Cycle 1 Day 1, 2, 3, 8; Cycle 2, 3, 4, 5 and 6 Day1)
研究者
研究点 (2)
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