A Multicenter, Phase 2 Study Evaluating IMC-A12 in Combination With Sorafenib as First-Line Therapy for Patients With Advanced Hepatocellular Carcinoma (HCC)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
To determine if IMC-A12 given in combination with Sorafenib is safe and effective for participants with advanced liver cancer.
详细描述
The purpose of this study is to determine progression-free survival (PFS) in participants with unresectable hepatocellular carcinoma who have received no prior systemic therapy when treated with IMC-A12 administered every three weeks in combination with oral sorafenib administered twice daily.
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
- •The participant has histologically or cytologically confirmed, unresectable HCC
- •The participant has at least one target lesion measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines. Target lesion(s) must not lay within a previously irradiated, ablated, or chemoembolized area. If a 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 not received prior systemic therapy for HCC. Participants may have received prior embolization, chemoembolization, intra-arterial chemotherapy infusion, ethanol injection, radiofrequency ablation, or cryosurgery
- •The participant has fasting serum glucose <160 milligrams/deciliter (mg/dL) or below the upper limit of normal (ULN) and/or hemoglobin A1C <7%. If baseline nonfasting glucose <160 mg/dL, fasting glucose measurement is not required
- •The participant has the ability to understand and the willingness to sign a written informed consent document
排除标准
- •The participant has brain metastases
- •The participant has acute hepatitis
- •The participant has poorly controlled diabetes mellitus. Participants with a history of diabetes mellitus are allowed to participate, provided that their blood glucose is within normal range and that they are on a stable dietary or therapeutic regimen for this condition
- •The participant has congestive heart failure > class II New York Heart Association (NYHA), unstable angina pectoris, new onset of angina pectoris, myocardial infarction within the past 6 months, or cardiac ventricular arrhythmias requiring antiarrhythmic therapy
- •The participant has experienced a hemorrhage or bleeding event ≥ National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade 3 within 4 weeks prior first dose of study therapy
研究组 & 干预措施
Cohort 1, IMC A12 - 10 mg/kg
Treatment cycles will repeat until there is evidence of progressive disease (PD), toxicity, or withdrawal. If any participant experiences a dose-limiting toxicity (DLT), an additional 3 participants will be enrolled at this dose level (for a total of 6). If no further DLTs, enrollment into Cohort 2 will occur.
干预措施: IMC-A12 (cixutumumab) - 10 milligrams/kilogram (mg/kg) (Biological)
Cohort 1, IMC A12 - 10 mg/kg
Treatment cycles will repeat until there is evidence of progressive disease (PD), toxicity, or withdrawal. If any participant experiences a dose-limiting toxicity (DLT), an additional 3 participants will be enrolled at this dose level (for a total of 6). If no further DLTs, enrollment into Cohort 2 will occur.
干预措施: Sorafenib (Drug)
Cohort 2, IMC A12 20 - mg/kg
Treatment cycles will repeat until there is evidence of PD, toxicity, or withdrawal.
干预措施: IMC-A12 (cixutumumab) - 20 mg/kg (Biological)
Cohort 2, IMC A12 20 - mg/kg
Treatment cycles will repeat until there is evidence of PD, toxicity, or withdrawal.
干预措施: Sorafenib (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Date of first dose of study drug up PD or death up to 12 months
PFS is defined as the time from date of first dose of study drug until the date of objective PD or death due to any cause, whichever occurs first. PD defined as a ≥20% increase in the sum of the longest diameter (LD) of target lesions using as reference the smallest sum LD since baseline or ≥1 new lesions. Participants who died without PD were considered to have progressed on the date of death. Participants who were alive and without PD were censored at the time of the last objective tumor assessment. Participants who did not progress and are subsequently lost to follow-up were censored at the date of their last objective tumor assessment before loss to follow-up. Participants who progressed or died after ≥2 missed tumor assessment visits were censored at the date of their last objective tumor assessment before missed assessments. Participants who begin a new anticancer therapy were censored at the date of their last objective tumor assessment before initiation of new therapy.
次要结局
- PK: Minimum Concentration (Cmin) Cycle 1(Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2))
- PK: Cmax Cycle 3(Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4))
- PK: Half-Life (t1/2) Cycle 1(Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2))
- PK: Clearance (CL) Cycle 1(Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2))
- PK: t1/2 Cycle 3(Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4))
- PK: Cmin Cycle 3(Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4))
- PK: AUC Cycle 3(Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4))
- PK: Vss Cycle 3(Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4))
- Percentage of Participants With Complete Response (CR) and Partial Response (PR) [Objective Response Rate (ORR)](Date of first dose of study drug to PD up to 12 months)
- Time to Disease Progression (TTP)(Date of first dose of study drug to date of PD up to 12 months)
- The Number of Participants With Serum Anti-Cixutumumab Antibody Assessment (Immunogenicity)(Predose, immediately prior to the first Cycle 3 and Cycle 5 infusions (3-week cycle) and 30 days after last dose of study drug)
- Number of Participants With Adverse Events (AEs)(First day of treatment up to 22 months)
- Pharmacokinetic (PK): Maximum Concentration (Cmax) Cycle 1(Cycle 1, Day 1: Predose, 1 hour (h), 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2))
- PK: Area Under the Concentration Versus Time Curve (AUC) Cycle 1(Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2))
- PK: Volume of Distribution at Steady State (Vss) Cycle 1(Cycle 1, Day 1: Predose, 1 h, 2 h, 168 h, 336 h, and 504 h after start of infusion (immediately prior to Cycle 2))
- PK: CL Cycle 3(Cycle 3, Day 1: Predose, 2 h, 24 h, 48 h, 72 h, 168 h, 240 h, 336 h and 504 h after start of infusion (immediately prior to Cycle 4))
- Overall Survival (OS)(Date of first dose of study drug to date of death up to 22 months)
- Duration of Response (DOR)(Date of first occurrence of CR or PR to first date of PD or death up to 8 months)