NCT05313282

A Trial of Hepatic Arterial Infusion Combined With Apatinib and Camrelizumab Versus Apatinib and Camrelizumab for C-staged Hepatocellular Carcinoma in BCLC Classification

A Randomized Controlled, Open-label, Multicenter Phase III Clinical Trial to Evaluate the Effectiveness and Safety of Hepatic Arterial Infusion Chemotherapy (HAIC) of Oxaliplatin, 5-fluorouracil and Leucovorin (mFOLFOX7) Combined With Apatinib and Camrelizumab Versus Apatinib and Camrelizumab for C-staged Hepatocellular Carcinoma in BCLC Classification.

• Status: Unknown
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 140 (estimated)
• Sponsor: Sun Yat-sen University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study was designed to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy combined with Apatinib and Camrelizumab (treatment group) versus Apatinib and Camrelizumab (control group) for C-staged Hepatocellular Carcinoma in BCLC classification. The primary outcome measure is to evaluate the progression-free-survival (PFS) of treatment group and control group for C-staged Hepatocellular Carcinoma in BCLC classification. The secondary Outcome measures include the overall survival (OS), time to progress (TTP), time-to-response (TTR), duration of response (DOR), objective response rate (ORR) and disease control rate (DCR) of treatment group and control group for C-staged Hepatocellular Carcinoma in BCLC classification. Moreover, this study aims to assess the safety and tolerability of treatment group and control group for C-staged Hepatocellular Carcinoma in BCLC classification.

Detailed description

Primary liver cancer is a common malignant tumor of the digestive system in the world. There are about 854,000 new incidences and 810,000 mortality each year. In China, there is a high incidence of liver cancer, with about 466,000 new cases and 422,000 mortality each year. Hepatocellular carcinoma (HCC) accounted for about 90% of primary liver cancer in pathological type. Most patients have reached advanced stage or with distant metastasis when diagnosed and the natural median survival time is only 3 to 4 months. Then only systemic therapy is recommended for patients in advanced HCC in many global guidelines. Hepatic arterial infusion chemotherapy (HAIC) of mFOLFOX7, anti-angiogenic targeting drugs, and antibody immunotherapy against programmed death molecule-1 (PD-1) immunological checkpoints are effective treatment options for advanced hepatocellular carcinoma. Many clinical studies have shown that the two-two combination of the above three treatment options can improve the anti-tumor overall response rate, the survival rate and even achieve clinical complete remission of patients with advanced HCC. Shi Ming et al reported HAIC combined with systemic targeted therapy has a better survival outcome compared to systemic targeted therapy mono-therapy \[OS 13.37 vs 7.13 months, PFS 7.03 vs 2.6 months\] in JAMA Oncology. Although the toxicity of combination therapy is slightly higher than that of sorafenib monotherapy, these adverse effects are tolerable. In addition, in a phase Ib study of Camrelizumab combined with apatinib in the treatment of advanced liver cancer, gastric cancer or gastroesophageal junction cancer showed that in 16 patients with HCC, the ORR was 50.0% and the DCR was 93.8%. When the dose of apatinib was 250 mg, the median PFS was 7.2 months. Camrelizumab combined with low dose apatinib can effectively reduce the incidence of adverse reactions, ≥10% of patients have treatment-related adverse reactions (all levels), no treatment-related adverse reactions leading to death. Therefore, low-dose anti-angiogenic drugs can inhibit tumor angiogenesis on the one hand, reduce immunosuppression by inducing normalization of blood vessels, enhance effector immune cell infiltration, and enhance anti-tumor immunity. In summary, for patients of C-staged Hepatocellular Carcinoma, HAIC, anti-angiogenic targeted therapy, and anti-PD-1 immunotherapy have their important status, and the combination of any two treatments brings about synergy effect. Then, could the combination of the three treatment methods further improve the outcome of advanced hepatocellular carcinoma? A phase-II study conducted by our team revealed that a combination of hepatic arterial infusion chemotherapy, targeted drugs (Apatinib), and anti-PD-1 immunotherapy (Camrelizumab) showed promising clinical benefits and acceptable safety for BCLC Stage C HCC, as the confirmed ORR was 61.54% per RECIST 1.1. However, there is no prospective randomized study to prove the efficacy and safety of HAIC combined with apatinib and camrelizumab. So this study was designed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy combined with Apatinib and Camrelizumab versus Apatinib and Camrelizumab to provide a more effective and toxic-tolerable treatment for patients in C-staged Hepatocellular Carcinoma in BCLC classification.

Conditions

• C-staged Hepatocellular Carcinoma in BCLC Classification

Interventions

Type	Name	Description
COMBINATION_PRODUCT	Hepatic Arterial Infusion combined with Apatinib and Camrelizumab	Drug: FOLFOX Protocol (Oxaliplatin, fluorouracil, and leucovorin); Camrelizumab for injection and Apatinib-Mesylate Tablets Procedure: 1. On the first day of treatment, HAIC was conducted through a catheter intubated into the tumor feeding artery under DSA guidance with the following chemotherapeutic drugs (mFOLFOX7, oxaliplatin 85 mg/m2 2 hours, folinic acid 400 mg/m2, 5-FU 2500 mg/m2 46 hours) pumped into the tumor artery. The HAIC is repeated every 3 weeks. The cumulative maximum sessions of HAIC is up to 6 times. 2\. Taking Apatinib-Mesylate Tablets (250 mg/tablet) orally on the 8th day 30minutes after meals, once a day, for continuous medication. 3\. On the 22nd day of treatment, namely the second session of HAIC, intravenous infusion of Camrelizumab 200mg every 3 weeks. 4\. The cumulative maximum drug use period is up to 2 years. The patient is concurrent on medication until the treatment discontinuation criteria specified in the protocol appear.
COMBINATION_PRODUCT	Apatinib combined with Camrelizumab	Drug: Camrelizumab for injection and Apatinib-Mesylate Tablets Procedure: 1. Taking Apatinib-Mesylate Tablets (250 mg/tablet) orally 30minutes after meals, once a day, for continuous medication 2. Intravenous infusion of Camrelizumab 200mg every 2 weeks.

Timeline

• Start date: 2022-06-15
• Primary completion: 2024-11-01
• Completion: 2025-06-01
• First posted: 2022-04-06
• Last updated: 2022-06-16

Locations

5 sites across 1 country: China