A Phase 2b Randomized Trial of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) Plus Best Supportive Care Versus Best Supportive Care in Patients With Advanced Hepatocellular Carcinoma Who Have Failed Sorafenib Treatment
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 129
- 试验地点
- 38
- 主要终点
- Survival
研究概览
简要总结
This study is to determine whether JX-594 (Pexa-Vec) plus best supportive care is more effective in improving survival than best supportive care in patients with advanced Hepatocellular Carcinoma (HCC) who have failed sorafenib.
详细描述
This Phase 2b, open-label, randomized, multi-center study is designed to evaluate the efficacy and safety of JX-594 (Pexa-Vec) in patients with advanced hepatocellular carcinoma (HCC) who have previously failed sorafenib treatment. Eligible patients are randomly assigned in a 2:1 ratio to receive either the experimental therapy (JX-594 plus Best Supportive Care [BSC]) or the control therapy (BSC alone).
Patients assigned to the experimental arm receive an initial intravenous (IV) infusion of JX-594 on Day 1. This is followed by intratumoral (IT) injections of JX-594 directly into viable liver tumors under imaging guidance on Day 8, Day 22, and Weeks 6, 12, and 18. These patients will also receive BSC, but active anti-cancer treatments are strictly prohibited. In contrast, patients in the control arm receive only Best Supportive Care (e.g., hydration, nutrition, pain management) at the treating physician's discretion without any study drug injections. Experimental or active anti-cancer therapies are not permitted in the control arm.
The primary objective of this study is to compare the Overall Survival (OS) between the two treatment arms. Secondary objectives include evaluating Time-to-Tumor Progression (TTP) and objective response rate based on mRECIST criteria for HCC. The study also evaluates Time-to-Symptomatic Progression (TSP), which is defined by changes in the FACT Hepatobiliary Symptom Index (FHSI-8) questionnaire and ECOG performance status. Additionally, the study assesses changes in Quality of Life (QoL) measured by EORTC and FACT-Hep questionnaires. Finally, overall safety and tolerability are closely monitored through the incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) graded according to NCI CTCAE v4.03, along with clinical laboratory evaluations.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of primary HCC by tissue biopsy (histological/cytological diagnosis), or clinical diagnosis
- •Previously treated with sorafenib for ≥ 14 days and has discontinued sorafenib treatment at least 14 days prior to randomization due to either intolerance or radiographic progression NOTE: Sorafenib is NOT required to be the most recent treatment received for HCC
- •ECOG performance status 0, 1 or 2
- •Child-Pugh Class A; or Child-Pugh Class B7 without clinically significant ascites
- •Hematocrit ≥30% or Hemoglobin ≥10 g/dL
- •Tumor status: Measurable viable tumor in the liver and injectable under imaging-guidance; At least one tumor in the liver that has not received prior local-regional treatment OR that has exhibited >25% growth in viable tumor size since prior local-regional treatment.
排除标准
- •Received sorafenib within 14 days prior to randomization
- •Received systemic anti-cancer therapy other than sorafenib within 28 days of randomization
- •Prior treatment with JX-594
- •Platelet count < 50,000 PLT/ mm3
- •Total white blood cell count < 2,000 cells/mm3
- •Prior or planned organ transplant
- •Known significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication
- •Severe or unstable cardiac disease
- •Viable CNS malignancy associated with clinical symptoms
- •Pregnant or nursing an infant
- •History of inflammatory skin condition (e.g., eczema requiring previous treatment, atopic dermatitis)
研究组 & 干预措施
JX-594 + Best Supportive Care
Patients on Arm A will receive 1 e9 pfu (plaque forming units) total dose of JX-594 (Vaccinia GM-CSF / TK-deactivated Virus) on each of six (6) treatments over 18 weeks.
干预措施: JX-594 recombinant vaccina GM-CSF (Biological)
Best Supportive Care
Patients on the control arm (Arm B) will have best supportive care over 18 weeks.
干预措施: Best Supportive Care (Other)
结局指标
主要结局
Survival
时间窗: CT scan every six weeks until progression or death, assessed up to 21 months
Determine overall survival for patients receiving JX-594 plus best supportive care (Arm A) compared with those patients receiving best supportive care (Arm B) in patients with advanced hepatocellular carcinoma (HCC) who have failed sorafenib treatment.
次要结局
- Time to Tumor Progression(CT scan every six weeks until progression or death, assessed up to 21 months)
- Quality of Life(assessed up to 21 months (average))
- Tumor Response(CT scan every 6 weeks until progression or death, assessed up to 21 months (average))
- Safety profile of JX594(assessed up to 21 months (average))
- Time-to-symptomatic-progression(assessed up to 21 months (average))