Infusional FOLFOX Plus Camrelizumab and Apatinib vs HAIC-FOLFOX Plus Camrelizumab and Apatinib for Advanced HCC

Study Overview
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Brief Summary
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This is a multi-center randomized phase III clinical study of first-line intravenous FOLFOX plus Camrelizumab and apatinib versus HAIC-FOLFOX plus Camrelizumab and apatinib for BCLC C stage hepatocellular carcinoma.

Official Title
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Infusional FOLFOX Plus Camrelizumab and Apatinib Versus HAIC-FOLFOX Plus Camrelizumab and Apatinib for Hepatocellular Carcinoma of BCLC C Stage: A Multi-center Randomized Phase III Trial

Conditions
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BCLC Stage C Hepatocellular Carcinoma, Chemotherapy Effect

Intervention / Treatment
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* Drug: intravenous FOLFOX7 plus Camrelizumab and apatinib
* Drug: HAIC-FOLFOX plus Camrelizumab and apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients volunteered to participate in this study and signed informed consent; Age 18-75, male or female; ECOG PS score 0-2; Child-pugh liver function grading: Grade A or B The clinical diagnosis conforms to primary hepatocellular carcinoma (HCC) and the lesion conforms to BCLC stage C Did not received any type of other first-line drugs such as Sorafenib According to RECIST 1.1 standard, patients have at least one measurable lesion (CT/MRI scan long diameter ≥10mm or CT/MRI scan short diameter ≥15mm for lymph node lesions, and the lesion has not received radiotherapy, freezing or other local treatments); Expected survival ≥ 12 weeks; The function of vital organs meets the following requirements (excluding the use of any blood component and cell growth factor within 14 days): Blood routine:White blood cells count ≥3.0×10^9/L Platelet count ≥70×10^9/L Hemoglobin ≥80g/L(without blood transfusion); Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times upper limit of normal value (ULN); Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal value (ULN); AST or ALT levels ≤ 3 times the upper limit of normal value (ULN) Women of childbearing age should agree to use contraceptives (such as intrauterine devices, contraceptives or condoms) during and within six months of the end of medication;Patients with negative serum or urine pregnancy tests within 7 days prior to study inclusion and who must be non-lactating, and males should agree to use contraceptives during the study period and for 6 months after the end of the study period. Subjects have good compliance and cooperate with the follow-up. Subjects with HBV or HCV infection should receive anti-virus treatment without interfron. Exclusion Criteria: Have received immunotherapeutic drugs or interferon in the past. Severe allergic reaction to other monoclonal antibodies, immunotherapy or chemotherapy. Female subjects with pregnancy or on feeding. Patients with congenital or acquired immune deficiencies. Abnormal coagulation function (INR>2.0, PT>16s), have bleeding tendency or are receiving thrombolysis or anticoagulation therapy, and allow preventive use of low-dose aspirin and low-molecular-weight heparin The patient has suffered from other malignant tumors at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ) The patient has active infection, fever of unknown origin within 7 days (CTCAE>2) Patients with congenital or acquired immune deficiencies. With clinical symptoms or diseases of the heart that are not well controlled. According to the judgment of the investigator, the patients with factors that may affect the results of the study or cause the study to be terminated midway, such as alcoholism, drug abuse, other serious diseases (including mental illness) need to be treated together, severe laboratory abnormalities, accompanied by family or social factors, which will affect the safety of patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: arm1: infusional FOLFOX plus Camrelizumab and apatinib arm2: HAIC-FOLFOX plus Camrelizumab and apatinib
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infusional FOLFOX<br>Infusional mFOLFOX7 plus Camrelizumab and apatinib | Drug: intravenous FOLFOX7 plus Camrelizumab and apatinib<br>* Leucovorin 200mg/m2 administered IV on Days 1 of a 21 day cycle Oxaliplatin 85 mg/m2 IV on Days 1 of a 21 day cycle Fluorouracil 5-FU continuous infusion: 400mg/m2 on D1 and then 2400mg/m2 for 46h of each 21 day cycle. Camrelizumab 200mg infusion on D1 for every 21 days Apatinib 250mg，po，qd for every 21 days<br>|
| Active Comparator: HAIC-FOLFOX<br>HAIC-FOLFOX plus Camrelizumab and apatinib | Drug: HAIC-FOLFOX plus Camrelizumab and apatinib<br>* 2-h infusion of oxaliplatin at 85 mg/m2 ,a 2-3-h administration of leucovorin at 400 mg/m2 , and a 46-h delivery of fluorouracil at 2500 mg/m2. camrelizumab (200 mg intravenously, commencing in 7 days after the first HAIC cycle and repeated every 21 days) and apatinib (250 mg daily, taken orally, beginning in 7 days after the initial HAIC cycle) Camrelizumab 200mg infusion on D1 for every 21 days Apatinib 250mg，po，qd for every 21 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | objective response rate based on RECISTv1.1 | up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mORR | objective response rate based on mRECIST | up to approximately 3 years | 
| DOR | Proportion of patients who achieved complete response (CR) or partial response (PR) at the end of treatment, based on mRECIST criteria. Patients were evaluated once every 3 cycles during the 1st to 6th treatment cycle and once every 3 months during the sequential treatment phase. | up to approximately 3 years | 
| DCR | The percentage of patients whose tumors shrink or stabilize for a certain period of time, including complete response (CR), partial response (PR), and stable (SD) cases. Patients were evaluated once every 3 cycles during the 1st to 6th treatment cycle and once every 3 months during the sequential treatment phase. | up to approximately 3 years | 
| 1y-PFSR | The proportion of patients who did not develop tumor progression from enrollment to 1 year of follow-up. | 1 year | 
| 2y-OSR | Proportion of patients surviving from the start of enrollment to the full 2 years of follow-up. | 2 year | 
| OS | The time between the start of treatment and the patient's death | up to approximately 5 years | 
| PFS | The time from the start of treatment to the first progression of the patient's disease | up to approximately 3 years | 
| TRAE | The classification of adverse events during treatment was based on NCI-CTCAE v5.0 criteria. | up to approximately 3 years | 
| conversion rate | rate of unresectable converted into resectable | up to approximately 3 years |