NCT04947826Unknown2 期
A Randomized, Double-blinded, Controlled Phase II Study of Combination Therapy of HAIC (Hepatic Arterial Infusion Chemotherapy), HLX10 (PD-1 Antibody) and HLX04 (VEGF Antibody) Compared With HAIC and Placebo in Hepatocellular Carcinoma With Major Portal Vein Tumor Thrombosis
Shanghai Zhongshan Hospital0 个研究点目标入组 100 人开始时间: 2021年8月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 100
- 主要终点
- Objective response rate
研究概览
简要总结
This is a randomized, double-blinded, controlled, phase II study. The purpose is to evaluate efficacy and safety of the combination therapy of HAIC (Hepatic arterial infusion chemotherapy) with HLX10 (PD-1 antibody) and HLX04 (VEGF antibody) compared with HAIC and placebo in patients with hepatocellular carcinoma with major portal vein tumor thrombosis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Willing to attend the study and having given the ICF
- •Have a HCC diagnosis confirmed by radiology, histology, or cytology
- •HCC is diagnosed at Barcelona Clinic Liver Cancer (BCLC) Stage C with major portal vein tumor thrombosis ( VP3～4, or Cheng's II～IV)
- •Have not accepted any of systemic therapy for HCC such as systemic chemotherapy, molecular targeted drugs, immunotherapy.
- •At least 1 measurable intrahepatic lesion suitable for repeat assessments according to RECISTv1.1 criteria and it has not undergone surgery, radiology and/or other regional therapy (including but not limited to radiofrequency ablation, percutaneous ethanol injection, freezing therapy, high intensity focused ultrasound, transcatheter arterial chemoembolization, transcatheter arterial embolization). But if it progressed after the regional therapy, it could be selected as a target lesion. The local regional therapy must be done 4 weeks before randomization and the related AEs must recover to ≤ CTCAE grade
- •Child-Pugh score ≤7
- •Eastern Cooperative Oncology Group (ECOG) 0 or 1
- •Expected life time is over 12 weeks.
- •HBV-DNA < 2000 IU/mL
- •Organs function:
- •Platelet count ≥75×109/L Absolute neutrophil count (ANC) ≥1.5×109 /L White blood cell count ≥3.0×109 /L Haemoglobin ≥9.0 g/dL Serum total bilirubin ≤1.5×ULN ALT ≤5×ULN, and AST ≤5×ULN（ALT ≤3×ULN, and AST ≤3×ULN, if HCV-RNA is detectable） Albumin ≥28 g/L INR ≤1.5×ULN PT ≤1.5×ULN APTT ≤1.5×ULN Creatinine clearance (CL) >50 mL/min or serum creatinine ≤1.5×ULN Urine protein ≤1+ or ≤1.0g/24h
- •Patient is not fertile or willing and able to obey effective contraception.
排除标准
- •Known fibrolamellar HCC, sarcomatoid HCC, mixed cholangiocarcinoma and HCC
- •History of hepatic encephalopathy
- •History of GI bleeding within 6 months, or investigator defined with high risk of haemorrhage for esophageal varices
- •With distant metastasis (hilar lymph nodes metastasis is allowed)
- •Co-infection of HBV and HCV
- •History of other malignancy within 5 years except for healed local tumor.
- •History of or plan to accept allogenic organ transplantation
- •Ascites requiring invasive intervention (e.g. paracentesis) to maintain symptomatic control (every month or more often)
- •History of myocardial infarction or unstable angina or uncontrolled arrythmia or stroke or cerebral hemorrhage within 6 months prior to randomization. QTcF value ≥450ms（male）or ≥470ms（female） detected by 12-lead electrocardiogram.
- •New York Heart Association Grade ≥2 congestive heart failure or LVEF <50%
- •Uncontrolled hypertension
- •History of hypertensive crisis or hypertensive encephalopathy
- •Active infection including but not limited to tuberculosis and HIV
- •With interstitial lung disease, lung fibrosis, pneumoconiosis, radiation pneumonitis, drug-associated pneumonia and serious impairment in lung function
- •Active autoimmune disorders except patients with substitutional treatment with thyroid hormone and type I diabetes under treatment with insulin.
- •Receipt of live attenuated vaccine within 28 days prior to randomization
- •Current or prior use of steroids (>10mg/d prednisone) or immunosuppressive medication within 14 days before randomization
- •Significant traumatic injury or major surgical procedure within 28 days prior to randomization
- •Receipt of checkpoint inhibitors or T cell costimulatory drugs
- •Receipt of bevacizumab or its analogues
- •Involved in another clinical trial less than 14 days before randomization
- •Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
- •Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control
- •Active bleeding, with history of ≥grade 3 bleeding within 6 months, or ≥grade 2 bleeding within 3 months
- •Use of anti-thrombotics within 5 days prior to randomization
- •In need of NSAIDs for long-term treatment.
- •With one of the following diseases within 6 months before randomization:
- •(1) Digestive fistula, perforation and abscess (2) Gastrointestinal obstruction (3) Abdominal infection or inflammation (4) Major vascular disease
- •With severe and green wound, active ulcer or untreated fracture
- •History of drug abuse
- •Judgment by the Investigator that the patient should not participate in the study if the patient is unlikely to screen for the study
研究组 & 干预措施
HAIC + HLX10 + HLX04
Experimental
HAIC: FOLFOX, q3w, up to 8 times; HLX10: 4.5mg/kg, iv, q3w, up to 2 years; HLX04: 15.0mg/kg, iv, q3w, up to 2 years.
干预措施: HAIC (Hepatic arterial infusion chemotherapy) (Procedure)
HAIC + HLX10 + HLX04
Experimental
HAIC: FOLFOX, q3w, up to 8 times; HLX10: 4.5mg/kg, iv, q3w, up to 2 years; HLX04: 15.0mg/kg, iv, q3w, up to 2 years.
干预措施: HLX10 (PD-1 antibody) (Drug)
HAIC + HLX10 + HLX04
Experimental
HAIC: FOLFOX, q3w, up to 8 times; HLX10: 4.5mg/kg, iv, q3w, up to 2 years; HLX04: 15.0mg/kg, iv, q3w, up to 2 years.
干预措施: HLX04 (VEGF antibody) (Drug)
HAIC + Placebo
Placebo Comparator
HAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years.
干预措施: HAIC (Hepatic arterial infusion chemotherapy) (Procedure)
HAIC + Placebo
Placebo Comparator
HAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years.
干预措施: Placebo (Drug)
结局指标
主要结局
Objective response rate
时间窗: The proportion of patients with complete response or partial response, through study completion, an average of 3 years.
efficacy
次要结局
- Overall survival(From date of randomization until death from any cause, up to 48 months)
- Duration of response(From date of randomization until the date of first documented progression, up to 48 months)
- Time to response(From date of randomization until the date of first documented response, up to 48 months)
- Progression free survival rate at 12-month time point(From date of randomization until 12-month time point)
- Progression free survival(From date of randomization until the date of the first documented progression or date of death from any cause, whichever comes first, up to 48 months)
- Time to progression(From date of randomization until the date of first documented progression, up to 48 months)
- Overall survival rate at 12-month time point(From date of randomization until 12-month time point)
研究者
相似试验
已完成
2 期
To Assess the Efficacy and Safety of Ceftriaxone in Patients With Mild to Moderate Parkinson's Disease DementiaParkinson's Disease DementiaNCT03413384BrainX Corporation100
终止
2 期
Efficacy and Safety Study of SUNPG1622Active Ankylosing Spondylitis or Non-Radiographic Axial SpondyloarthritisNCT02980705Sun Pharmaceutical Industries Limited180
已完成
2 期
A Phase 2 Clinical Study of CU-20401Efficacy and SafetyNCT06194188Cutia Therapeutics（Wuxi）Co.,Ltd108
撤回
2 期
A Study Evaluating the Efficacy and Safety of Adjuvant Platinum-Doublet Chemotherapy, With or Without Atezolizumab, in Patients Who Are ctDNA Positive After Complete Surgical Resection of Stage IB to Select IIIB Non-Small Cell Lung CancerCarcinoma, Non-Small Cell LungNCT04611776Hoffmann-La Roche
已完成
2 期
Safety and Efficacy of Atrasentan in Men With Hormone Naive Prostate Cancer Exhibiting Early Signs of Biochemical FailureProstatic NeoplasmsNCT00038662Abbott200