An Open Label, Multicenter, Phase 2 Study Evaluating the Safety and Efficacy of IMC-1121B as First Line Monotherapy in Patients With Unresectable Hepatocellular Cancer
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 7
- 主要终点
- Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab
研究概览
简要总结
A study to determine how long ramucirumab (IMC-1121B) will stop cancer from growing in participants with liver cancer that cannot be treated with surgery.
详细描述
Inhibition of angiogenesis is considered a promising approach to the treatment of cancer. Members of the vascular endothelial growth factor (VEGF) family and the VEGF receptor-2 (VEGFR-2) are important mediators of angiogenesis and are likely important therapeutic targets in advanced hepatocellular cancer (HCC).
Angiogenesis appears integral to HCC development and pathogenesis. Angiogenesis inhibition has been efficacious in both in vitro and in vivo HCC models and results of clinical studies also suggest potential to inhibit disease growth.
Ramucirumab is a fully human monoclonal antibody (MAb) that specifically binds to the extracellular domain of VEGFR-2 with high affinity. Phase 1 studies currently nearing completion have demonstrated safety and tolerability at clinically relevant doses, with preliminary evidence of clinical efficacy in a variety of human cancers.
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
- •The participant must have histologically-confirmed, unresectable HCC
- •The participant has at least one unidimensionally-measurable target lesion [≥ 2 centimeters (cm) with conventional techniques, or ≥ 1 cm by spiral computed tomography (CT) or magnetic resonance imaging (MRI)], as defined by Response Evaluation Criteria in Solid Tumors (RECIST). Target lesion(s) must not lay within a previously irradiated, ablated, or chemoembolized area. If a target lesion does lie in such an area, there must be evidence of growth on successive imaging studies, including tumor hypervascularity, in order for such a lesion to be considered a target lesion
- •The participant has a Cancer of the Liver Italian Programme (CLIP) score of 0-3
- •The participant has a Child-Pugh Classification score of A or B (liver dysfunction)
- •The participant has provided signed informed consent
排除标准
- •The participant has received prior systemic chemotherapy, biologic or anti-angiogenic therapy, or investigational systemic therapy for HCC
- •The participant has had bleeding from esophageal or gastric varices during the 3 months prior to study participation. Note: If the participant has any history of known esophageal varices, or evidence of esophageal varices on CT/MRI, the participant must undergo endoscopic evaluation prior to study entry (minimally invasive capsule esophageal endoscopy is an acceptable initial modality). The participant with endoscopically detected esophageal varices is eligible provided he/she meets all other entry criteria. The participant with any history or current evidence of esophageal varices must receive oral beta-blocker therapy throughout participation while on study, he/she may receive optimal endoscopic therapy as determined by the consulting gastroenterologist or hepatologist, and must undergo regular endoscopic follow-up throughout participation while on study
- •The participant has acute hepatitis
- •The participant has central nervous system (CNS) metastases or carcinomatous meningitis
- •The participant has poorly-controlled hypertension [in other words (ie), blood pressure in abnormal range despite medical management]
结局指标
主要结局
Progression Free Survival (PFS) in Participants With Unresectable Hepatocellular Cancer Treated With the Monoclonal Antibody Ramucirumab
时间窗: First dose to date of progressive disease or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)]
PFS was defined as the time from the first day of therapy to the first evidence of disease progression or death from any cause. As classified according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria, disease progression was having at least a 20% increase in the sum of the longest diameter of target lesions and/or unequivocal progression of a non-target lesion and/or detection of a new lesion. Participants who were alive and without disease progression and participants who did not progress and were subsequently lost to follow-up were censored at the last objective tumor assessment.
次要结局
- Time to Progression(First dose to date of PD [every 3 cycles up to 18 months (1 cycle=2 weeks)])
- Overall Survival(First dose to death due to any cause up to 37.5 months)
- Percentage of Participants With Complete Response or Partial Response (Objective Response Rate)(First dose to date of objective progressive disease (PD) or death up to 18 months)
- Number of Participants With Serum Anti-Ramucirumab Antibodies(Prior to dosing at baseline, Cycles 4 and 7, and 30 days after end of therapy (1 cycle=2 weeks))
- Number of Participants With Drug-Related Treatment-Emergent Adverse Events(First dose to 37.5 months)
- Duration of Response(Time of first response (CR or PR) to disease progression, or death due to any cause [every 3 cycles up to 18 months (1 cycle=2 weeks)])