A Single-arm Clinical Study of HAIC Combined With Apatinib and Camrelizumab in the Treatment of Unresectable MTM HCC

Study Overview
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Brief Summary
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This is a single-arm, open, multicenter II phase clinical study to compare the efficacy and safety of HAIC combined with Apatinib and Camrelizumab in the treatment of unresectable middle-advanced MTM-HCC.

Detailed Description
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Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is a special pathological subtype of liver cancer, characterized by vascular invasion, early recurrence and poor survival. For unresectable MTM-HCC, there are currently no prospectively clinically validated treatment options. As a local interventional treatment, hepatic arterial infusion chemotherapy (HAIC) has shown better efficacy and safety than traditional transcatheter arterial chemoembolization (TACE) in the treatment of unresectable HCC. In addition, HAIC has been widely used as an alternative to sorafenib in advanced HCC in the eastern Asia. Studies have also shown that the combination of Apatinib and Camrelizumab has also shown encouraging results, and patients are well tolerated. Therefore, we designed HAIC combined with Apatinib and Camrelizumab for the exploratory study of unresectable MTM-HCC, in order to provide a safe, effective and tolerable option for patients with MTM-HCC, prolong their survival time and improve their quality of life. Study population: 38 untreated patients with unresectable middle-advanced macrotrabecular-massive hepatocellular carcinoma Treatment: All patients were treated with standard HAIC (administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries) on the first day (D1). Immediately after the first HAIC, the liver function was reexamined. If the liver function was grade Child-Pugh A, Camrelizumab was given intravenously once every 3 weeks (D1) on the same day, 200mg/, once every 3 weeks (D1). Apatinib capsule was given orally to 250mg within half an hour after breakfast on the second day (D2) after the first HAIC. The drug was given continuously once a day and stopped on the same day of each HAIC. The combination of drugs for 3 weeks is a cycle.The treatment continued until the patient developed the disease or met the other criteria for terminating the study. Curative effect evaluation： The tumor condition was evaluated by imaging method at D28 (±7 days) after each HAIC, until the curative effect was evaluated as PD or unsuitable for further treatment. After 3 times of HAIC treatment, the tumor efficacy was evaluated every 8 weeks (±3 days) after the first HAIC treatment until disease progression (Response Evaluation Criteria In Solid Tumors（RECIST）1.1) or death (during treatment) or toxicity intolerable. The tumor treatment and survival status after disease progression were recorded.

Official Title
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A Single-arm, Exploratory Clinical Study of Hepatic Arterial Infusion Chemotherapy (HAIC) Combined With Apatinib and Camrelizumab in the Treatment of Unresectable Macrotrabecular-massive Hepatocellular Carcinoma

Conditions
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Macrotrabecular Massive Hepatocellular Carcinoma

Intervention / Treatment
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* Procedure: HAIC
* Drug: Camrelizumab plus Apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Macrotrabecular Massive HCC diagnosed by histopathology or cytology according to the Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2022 Edition); Stage Ⅰa Ⅱb and up-to-seven（tumor number +tumor size≥7) OR stage Ⅲa according to the Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2022 Edition); Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; expected survival ≥ 12 weeks; Child-Pugh liver function class A-B7 Patients with newly diagnosed hepatocellular carcinoma who have not received any local or systemic treatment for hepatocellular carcinoma; At least one measurable lesion (according to RECIST1.1 standard); its diameter ≥ 1cm was accurately measured by magnetic resonance imaging (MRI) enhancement or computed tomography (CT) enhancement, and the target lesion had not received local treatment in the past (including not limited to hepatic arterial Infusion chemotherapy, radiofrequency ablation, argon-helium knife, radiotherapy, etc.); No serious organic diseases of heart, lung, brain and other organs; Exclusion Criteria: Women who are pregnant (positive for pre-medication pregnancy test) or breastfeeding Participated in clinical trials of other antineoplastic drugs within 4 weeks before entering the group. Received any surgery or invasive treatment or operation (except venous catheterization, puncture and drainage, etc.) within 4 weeks before the start of the group; History of previous immune and targeted therapy for HCC; Patients who have previously received organ transplants or planned organ transplants; Significant clinical gastrointestinal bleeding or a potential risk of bleeding was identified by the investigator during the 30 days prior to study entry. Active or uncontrolled severe infection (≥ （Common Terminology Criteria for Adverse Events）CTCAE 2 grade infection); Suffered from other malignant tumors in the past 5 years, except basal cell or squamous cell carcinoma of the skin after radical resection, or cervical carcinoma in situ; Any other disease, with clinically significant metabolic abnormalities, physical examination abnormalities or laboratory abnormalities, according to the researchers, there is reason to suspect that the patient has a disease or state that is not suitable for the use of research drugs (such as having seizures and requiring treatment), or will affect the interpretation of the results of the study, or put the patient at high risk; The researchers judged that patients have other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, and other serious diseases (including mental illness) that need to be combined with treatment. there are serious 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HAIC Combined With Apatinib and Camrelizumab<br>All patients were treated with standard HAIC on the first day (D1). Immediately after the first HAIC, the liver function was reexamined. If the liver function was grade Child-Pugh A, Camrelizumab was given intravenously once every 3 weeks (D1) on the same day, 200mg/, once every 3 weeks (D1). Apatinib capsule was given orally to 250mg within half an hour after breakfast on the second day (D2) after the first HAIC. The drug was given continuously once a day and stopped on the same day of each HAIC. The combination of drugs for 3 weeks is a cycle.The treatment continued until the patient developed the disease or met the other criteria for terminating the study. | Procedure: HAIC<br>* administration of oxaliplatin , fluorouracil, and leucovorin via the tumor feeding arteries every 3 weeks.<br>* Other names: hepatic arterial infusion chemotherapy of FOLFOX;Drug: Camrelizumab plus Apatinib<br>* Apatinib(250 mg; p.o.; qd.); camrelizumab (200 mg; iv drip; q3w) If the liver function was grade Child-Pugh A, Camrelizumab was given intravenously once every 3 weeks (D1) on the same day, 200mg/, once every 3 weeks (D1). Apatinib capsule was given orally to 250mg within half an hour after breakfast on the second day (D2) after the first HAIC. The drug was given continuously once a day and stopped on the same day of each HAIC.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective remission rate (ORR) | Refers to the proportion of patients whose tumors have shrunk to a certain amount and maintained for a certain period of time, including cases of complete remission (CR), partial remission (PR). | After the first HAIC treatment, until the disease progresses or dies (during the treatment of the patient) or the toxicity is intolerable，through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | Refers to the date from the date of admission to the date of the first progression of disease or death of any cause. | From date of the first HAIC treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 
| Disease control rate (DCR) | Percentage of confirmed cases including complete remission (CR), partial remission (PR) and disease stability (SD) among patients with evaluable efficacy | From date of the first HAIC treatment until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 12 months | 
| Total Survival time (OS) | Refers to the date from the date of admission to the date of death of any cause | Through study completion, an average of 2 year | 
| Incidence of adverse events and toxicities of Apatinib in combination with Camrelizumab | Categorized according to NCI Common Toxicity Criteria version 5.0. Summarized in terms of type, severity (grade 1-5), and dose level in tabular format. | Until the last medication for 30 days (±7 days) or before the start of other anti-tumor therapy (whichever occurs first). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAIC, Camrelizumab, Apatinib