A Phase I/II Study of Bavituximab and Sorafenib In Patients With Advanced Hepatocellular Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up.
研究概览
简要总结
This is a non-randomized, open-label, single-institution phase I/II therapeutic trial of bavituximab and sorafenib in patients with advanced hepatocellular carcinoma (HCC). This study will be activated at the UT Southwestern Medical Center, comprised of The Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Hospitals-St. Paul and Parkland Memorial Hospital System. Advanced HCC is defined as disease that is not amenable to surgical resection or orthotopic liver transplantation or is metastatic in nature.
详细描述
The investigators are looking for men or women aged 18 years or older with hepatocellular carcinoma not suitable for surgical resection or hepatic transplantation. Prior locoregional therapy including but not limited to transarterial chemoembolization (TACE), radiofrequency ablation (RFA) or ethanol injection is allowed as long as the treatment was 4 weeks previous. Patients must be Child-Pugh A with no previous treatment with sorafenib or other vascular endothelial growth factor (VEGF) inhibitors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Patients must have a diagnosis of hepatocellular carcinoma by at least one criterion listed below:
- •Histologically confirmed.
- •MRI or CT consistent with liver cirrhosis and at least one solid liver lesion >2 cm with early enhancement and delayed enhancement washout regardless of AFP.
- •AFP >400 ng/ml and evidence of at least one solid liver lesion >2 cm regardless of specific imaging characteristics on CT or MRI.
- •Locally advanced or metastatic disease.
- •Patients with locally advanced disease must have disease deemed to be unresectable or not eligible for hepatic transplantation. Determination will occur in the weekly GI DMT meeting by surgical oncologists and transplant surgeons.
- •Measurable disease, as defined as lesions that can accurately be measured in at least one dimension (longest diameter to be measured) according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1) at least 2 cm with conventional techniques or at least 1 cm with spiral computed tomography.
- •Child-Pugh Score A.
- •Age ≥ 18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-
- •Absolute neutrophil count ≥ 1,500 cells/mm
- •Platelet count ≥ 75,000 cells/mm
- •Total bilirubin ≤ 3.0 mg/dl.
- •Hemoglobin ≥ 8.5 g/dl.
- •AST and ALT ≤ 5.0 times upper limit of normal.
- •D-dimer ≤ 3 times upper limit of normal.
- •INR ≤ 1.8 (therapeutic anticoagulation allowed as long as medically indicated.
排除标准
- •History of bleeding diathesis or coagulopathy.
- •Symptomatic or clinically active brain metastases.
- •Major surgery within previous 4 weeks.
- •History of thromboembolic events (including both pulmonary embolisms and deep vein thrombosis); central venous catheter-related thrombosis > 6 months prior is allowed.
- •Prior adjuvant therapy with sorafenib or other Raf/MEK/RAS or VEGFR inhibitors. Prior adjuvant therapy is allowed provided it was completed > 6 months ago and there is documented recurrence of hepatocellular carcinoma.
研究组 & 干预措施
Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily
Cohort 1: Participants were administered Bavituximab:0.3 mg/kg weekly Sorafenib: 400mg PO twice daily
干预措施: bavituximab (0.3 mg/kg) and sorafenib (Drug)
Bavituximab: 1.0 mg/kg weekly Sorafenib: 400mg PO twice daily
Cohort 2: Participants were administered Bavituximab:1.0 mg/kg weekly Sorafenib: 400mg PO twice daily
干预措施: bavituximab (1.0 mg/kg ) and sorafenib (Drug)
Bavituximab: 3.0 mg/kg weekly Sorafenib: 400mg PO twice daily
Cohort 3: Participants were administered Bavituximab:3.0 mg/kg weekly Sorafenib: 400mg PO twice daily
干预措施: bavituximab (3.0 mg/kg) and sorafenib (Drug)
结局指标
主要结局
Median Radiographic Time to Progression (TTP) Calculated From Treatment Initiation to First Evidence of Disease Progression or Last Follow-up.
时间窗: Treatment initiation to first evidence of disease progression or last follow-up, an average of 24 months
Median radiographic time to progression (TTP) was calculated from treatment initiation to first evidence of disease progression or last follow-up by using the Kaplan-Meier method. The 95% confidence intervals (CIs) for time-to-progression data was calculated using Greenwood's formula.
Number of Patients With Dose Limiting Toxicity
时间窗: 8 months.
Dose limiting toxicity by serious adverse events by CTCAE version 4.0
次要结局
- Median Months of Disease Specific Survival Calculated From Treatment Initiation to Death From Advanced HCC (Hepatocellular Carcinoma) or Last Follow-up.(Treatment initiation to first evidence of death from advanced liver cancer or last follow-up, an average of 12 months)
- Median Months of Overall Survival Calculated From Treatment Initiation to Death or Last Follow-up.(Treatment initiation to death or last follow-up, an average 24 months)
- Safety, as Measured by the Number of Patients With Adverse Event Related to the Treatment That Experienced Grade 3 or Greater.(Up to 3 months of patient enrollment (phase 1))
研究者
Adam Yopp
Associate Professor of Medicine
University of Texas Southwestern Medical Center