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
Overview
- Phase
- Phase 2
- Intervention
- HAIC (Hepatic arterial infusion chemotherapy)
- Conditions
- Hepatocellular Carcinoma With Major Portal Vein Thrombosis
- Sponsor
- Shanghai Zhongshan Hospital
- Enrollment
- 100
- Primary Endpoint
- Objective response rate
- Last Updated
- 4 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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:
Exclusion Criteria
- •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%
Arms & Interventions
HAIC + HLX10 + HLX04
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.
Intervention: HAIC (Hepatic arterial infusion chemotherapy)
HAIC + HLX10 + HLX04
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.
Intervention: HLX10 (PD-1 antibody)
HAIC + HLX10 + HLX04
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.
Intervention: HLX04 (VEGF antibody)
HAIC + Placebo
HAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years.
Intervention: HAIC (Hepatic arterial infusion chemotherapy)
HAIC + Placebo
HAIC: FOLFOX, q3w, up to 8 times; Placebo1: saline, iv, q3w, up to 2 years; Placebo2: saline, iv, q3w, up to 2 years.
Intervention: Placebo
Outcomes
Primary Outcomes
Objective response rate
Time Frame: The proportion of patients with complete response or partial response, through study completion, an average of 3 years.
efficacy
Secondary Outcomes
- 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)