This study was designed to evaluate the effectiveness and safety of hepatic arterial infusion chemotherapy combined with Bevacizumab and Sintilimab (Triplet-combined Therapy) for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. The primary outcome measure is to evaluate the objective response rate (ORR RECIST 1.1) of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. The secondary Outcome measures include the objective response rate (ORR mRECIST 1.1), duration of response (DOR), disease control rate (DCR), progression-free survival rate (PFSR) \[ Time Frame: 6- and 12-month\], overall survival rate (OSR) \[ Time Frame: 6- and 12-month\], the median progression-free survival time (mPFS) and median overall survival time (mOS) of Triplet-combined Therapy for Unresectable A-staged Hepatocellular Carcinoma in BCLC classification. Moreover, this study aims to assess the safety and tolerability of Triplet-combined Therapy for Unresectable A-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 are unresectable 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 unresectable HCC. Shi Ming et al reported HAIC combined with systemic targeted therapy has a better survival outcome compared to systemic targeted therapy monotherapy \[OS 13.37 vs 7.13 months, PFS 7.03 vs 2.6 months\] in JAMA Oncology. In summary, for patients of unresectable Hepatocellular Carcinoma, HAIC, antiangiogenic 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 unresectable hepatocellular carcinoma? This study was designed to evaluate the efficacy and safety of a combination of hepatic arterial infusion chemotherapy, targeted drugs (Apatinib), and anti-PD-1 immunotherapy (Camrelizumab) to provide a more effective and toxic-tolerable treatment for patients in unresectable A-staged Hepatocellular Carcinoma in BCLC classification. This is a single-arm phase II study, and 30 patiented will be enrolled. The patients will receive Hepatic Arterial Infusion(mFOLFOX7) on the first day, and intravenous infusion of Bevacizumab on the 4th day, and intravenous infusion of Sintilimab on the 25th day. The intervention is repeated every 3 weeks. The primary outcome measure is ORR by RECIST 1.1.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
The patient will receive Hepatic Arterial Infusion(mFOLFOX7) on the first day, and intravenous infusion of Bevacizumab on the 4th day, and intravenous infusion of Sintilimab on the 25th day. The intervention is repeated every 3 weeks.
Yang-Kui Gu
Guangzhou, Guangdong, China
RECRUITINGSun Yat-Sen Memorial Hospital
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGNanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
NOT_YET_RECRUITINGThe Third Affiliated Hospital of Sun Yat-Sen University
Guanzhou, Guangdong, China
NOT_YET_RECRUITINGXiangya Hospital of Central South University
Changsha, Hunan, China
NOT_YET_RECRUITINGObjective response rate (ORR) by RECIST 1.1
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1
Time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)
Objective response rate (ORR) by mRECIST
ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by mRECIST
Time frame: From date of first dose of study drug until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)
The disease control rate (DCR)
DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST
Time frame: From date of first dose of study drug until disease progression, stable disease, development of unacceptable toxicity, withdrawal of consent, or sponsor termination (up to approximately 3 years)
Duration of response (DOR) by RECIST 1.1 and mRECIST
DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression or death (whichever occurs first) as assessed by RECIST 1.1 and mRECIST
Time frame: From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to approximately 3 years)
The progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST
Time frame: From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 3 years)
The overall survival rate (OSR)
Time frame: From date of first dose of study drug to the date of first documentation of death from any cause, whichever occurs first (up to approximately 3 years)
The progression-free survival time (mPFS)
The progression-free survival time (mPFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1 and mRECIST
Time frame: From date of first dose of study drug to the date of first documentation of disease progression (up to approximately 3 years)
The median overall survival time (mOS)
OS is measured from the start date of the Treatment Phase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date, whichever comes earlier.
Time frame: From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)
Surgical conversion rate
Time frame: From the start date of the Treatment Phase until date of Surgical resection(up to approximately 20 weeks)
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)
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