C-staged Hepatocellular Carcinoma in BCLC Classification Clinical Trial
Official title:
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.
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.
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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT04191889 -
A Trial of Hepatic Arterial Infusion Combined With Apatinib and Camrelizumab for C-staged Hepatocellular Carcinoma in BCLC Classification
|
Phase 2 |