Exploratory Open Label Dose-escalation Phase Ib Study to Evaluate Safety, Pharmacokinetics and Therapeutic Activity of RO5323441, Administered Intravenously, in Combination With Sorafenib (Nexavar®), in Patients With Advanced or Metastatic and/or Unresectable Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 主要终点
- Part I: Determination of recommended Part II dose
研究概览
简要总结
This open-label study will assess the safety, efficacy and pharmacokinetics of RO5323441 in combination with sorafenib in patients with advanced or metastatic hepatocellular carcinoma previously untreated with systemic therapy. In the dose-finding Part I, cohorts of patients will receive escalating doses of RO5323441 intravenously (iv) every 2 weeks in combination with sorafenib 400 mg orally twice daily. In the exploratory Part II, patients will be randomized to receive either the previously established dose of RO5323441 iv every 2 weeks plus continuous oral sorafenib or sorafenib alone. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs. For patients in the sorafenib arm with disease progression crossover to combination treatment with RO5323441 will be allowed.
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
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients >/= 21 years of age
- •Advanced or metastatic and/or unresectable hepatocellular carcinoma
- •At least 1 measurable lesion according to RECIST criteria
- •Primary tumor in situ (Expansion Cohort Part I, Part II)
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Adequate bone marrow, liver and renal function
排除标准
- •Prior systemic treatment for metastatic hepatocellular carcinoma or patients who had tumor removed (Expansion Cohort Part I, Part II)
- •Major surgery within previous 4 weeks or planned major surgical procedure during course of study
- •Radiation therapy within 28 days prior to start of study treatment
- •Serious non-healing wound, ulcer ore bone fracture
- •History of uncontrolled seizures or encephalopathy within the last 6 months
- •Current central nervous system (CNS) metastases or spinal cord compression
- •History of gastrointestinal perforation or esophageal/gastric bleeding within 6 months prior to study enrollment
- •History of another primary malignancy and off treatment for </= 3 years, except for non-melanoma skin cancer and carcinoma in situ of the cervix
- •Patients with prior liver transplant
- •Inadequately controlled hypertension or prior history of hypertensive crisis or hypertensive encephalopathy
- •Active bleeding diathesis
研究组 & 干预措施
Part I
干预措施: RO5323441 (Drug)
Part I
干预措施: sorafenib (Drug)
Part II (A)
干预措施: RO5323441 (Drug)
Part II (A)
干预措施: sorafenib (Drug)
Part II (B)
干预措施: sorafenib (Drug)
结局指标
主要结局
Part I: Determination of recommended Part II dose
时间窗: up to 12 months
Part II: Safety/tolerability: Incidence of adverse events
时间窗: up to 28 months
Part I : Safety/dose-limiting toxicity: Incidence of adverse events
时间窗: up to 12 months
次要结局
- Impact on wound healing (skin biopsies)(up to 40 months)
- Pharmacodynamic biomarkers (DCE-Magnetic Resonance Imaging evaluations, Placental Growth Factor, Vascular Endothelial Growth Factor Receptors)(up to 40 months)
- Pharmacokinetics of sorafenib in combination with RO5323441(up to 12 months)
- Safety: additional anti-drug antibodies sampling after termination of study drug treatment(2 and 4 months after last dose of study drug)
- Pharmacokinetics of RO5323441 in combination with sorafenib(up to 40 months)
- Efficacy: tumor assessments by Magnetic Resonance Imaging or Computed Tomography according to RECIST criteria(up to 40 months)