TACE Plus HAIC With Oxaliplatin and Raltitrexed for BCLC Stage C HCC

Study Overview
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Brief Summary
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Purpose：explore the effectiveness and safety of transarterial chemoembolization (TACE) plus Hepatic Arterial Infusion Chemotherapy (HAIC) with oxaliplatin and raltitrexed for Barcelona stage C hepatocellular carcinoma (HCC)

Detailed Description
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Thhis is a non-randomized, open, single-arm clinical study. patients receive cTACE+HAIC (oxaliplatin, raltitrexed) treatment, 6-8 weeks as a cycle, until the disease progresses, intolerable toxicity occurs, the patient is lost to follow-up or death, or situations other judged by researchers which treatment should be stopped. Number of patients: 66 patients End points：primary end points：safety 、objective response rate，disease control rate，progression free overall survival，second end point ：overall survival Include criteria： Volunteer to participate and sign the informed consent in writing; Age: 18-75 years old; No gender limit; BCLC stage C hepatocellular carcinoma with pathological diagnosis or clinical diagnosis; Barcelona stage C patients who failed first-line treatment (including but not limited to sorafenib, levatinib, atelizumab combined with bevacizumab, etc.); they have not received sorafenib in the past The patients treated by Sorafenib can receive sorafenib treatment at the same time, and the patients who have received sorafenib treatment progress can also receive regorafenib treatment. At least one measurable lesion (according to mRECIST criteria) imaging diagnosis time ≤ 21 days from selection; Child-pugh grade A-B7 grade The expected survival period is ≥3 months; ECOG Performance Status (ECOG) 0-2; Sufficient bone marrow hematopoietic function (within 7 days): hemoglobin ≥9 g/dL, white blood cells ≥3.0×109/L, neutrophils ≥1.5x109/L, platelets ≥80x109/L; liver and kidney functions are normal (Within 14 days): TBIL≤1.5 times the upper limit of normal; ALT and AST≤5 times the upper limit of normal; creatinine≤1.5 times the upper limit of normal; INR<1.7 or prolonged PT<4s Exclude criteria: Those who are currently receiving other effective treatments; Patients who have received oxaliplatin and raltitrexed in the past; Patients who have participated in other clinical trials within 4 weeks before enrollment; Unable to cooperate with cTACE and HAIC treatment; Patients with primary malignant tumors other than hepatocellular carcinoma at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ; Clinically significant cardiovascular diseases, such as heart failure (NYHA III-IV), uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or a history of myocardial infarction within the past 1 year; Neurological or mental abnormalities that affect cognitive ability, including central nervous system transfer; There were active serious clinical infections (>grade 2 NCI-CTCAE version 4.0), including active tuberculosis within 14 days before enrollment; Known or self-reported HIV infection; Uncontrolled systemic diseases, such as poorly controlled diabetes; Known to have hypersensitivity or allergic reactions to any component of the study drug; Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding Treatment：patients receive cTACE+HAIC (oxaliplatin, raltitrexed) treatment, 6-8 weeks as a cycle, until the disease progresses, intolerable toxicity occurs, the patient is lost to follow-up or death, or situations other judged by researchers which treatment should be stopped.

Official Title
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A Phase II Clinical Study of Transarterial Chemoembolization (TACE) Plus Hepatic Arterial Infusion Chemotherapy (HAIC) With Oxaliplatin and Raltitrexed for Barcelona Stage C Hepatocellular Carcinoma (HCC)

Conditions
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Transarterial Chemoembolization, Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: cTACE-HAIC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Volunteer to participate and sign the informed consent in writing; Age: 18-75 years old; No gender limit; BCLC stage C hepatocellular carcinoma with clear pathological diagnosis or clinical diagnosis; Barcelona stage C patients who failed first-line treatment (including but not limited to sorafenib, levatinib, atelizumab combined with bevacizumab, etc.); they have not received sorafenib in the past The patients treated by Sorafenib can receive sorafenib treatment at the same time, and the patients who have received sorafenib treatment progress can also receive regorafenib treatment. At least one measurable lesion (according to mRECIST criteria) imaging diagnosis time ≤ 21 days from selection; Child-pugh grade A-B7 grade The expected survival period is ≥3 months; General physical condition (ECOG) 0-2; Sufficient bone marrow hematopoietic function (within 7 days): hemoglobin ≥9 g/dL, white blood cells ≥3.0×109/L, neutrophils ≥1.5x 109/L, platelets ≥80x 109/L; liver and kidney functions are normal (Within 14 days): TBIL≤1.5 times the upper limit of normal; ALT and AST≤5 times the upper limit of normal; creatinine≤1.5 times the upper limit of normal; INR<1.7 or prolonged PT<4s Exclusion Criteria: Those who are currently receiving other effective treatments; Patients who have received oxaliplatin and raltitrexed in the past; Patients who have participated in other clinical trials within 4 weeks before enrollment; Unable to cooperate with cTACE and HAIC treatment; Patients with primary malignant tumors other than hepatocellular carcinoma at the same time, except for cured skin basal cell carcinoma and cervical carcinoma in situ; Clinically significant cardiovascular diseases, such as heart failure (NYHA III-IV), uncontrolled coronary heart disease, cardiomyopathy, arrhythmia, uncontrolled hypertension or a history of myocardial infarction within the past 1 year; Neurological or mental abnormalities that affect cognitive ability, including central nervous system transfer; There were active serious clinical infections (>grade 2 NCI-CTCAE version 4.0), including active tuberculosis within 14 days before enrollment; Known or self-reported HIV infection; Uncontrolled systemic diseases, such as poorly controlled diabetes; Known to have hypersensitivity or allergic reactions to any component of the study drug; Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding

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: cTACE-HAIC(oxaliplatin and raltitrexed)<br>Patients receive cTACE+HAIC (oxaliplatin, raltitrexed) treatment, 6-8 weeks as a cycle | Drug: cTACE-HAIC<br>* transarterial chemoembolization (TACE) plus Hepatic Arterial Infusion Chemotherapy (HAIC) with oxaliplatin and raltitrexed for Barcelona stage C hepatocellular carcinoma (HCC)<br>* Other names: OXRI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate, ORR | The objective response rate (ORR) was defined as the complete response (CR) rate + the partial response (PR) rate | 6 months | 
| Disease control rate, DCR | disease control rate (DCR) was defined as the CR rate + the PR rate + the stable disease (SD) rate | 6 months | 
| Progression free overall survival，PFS | PFS was defined as the interval between the time at which treatment was initiated and intrahepatic tumor and/or extrahepatic tumor progression, symptomatic progression, including massive ascites and liver function that was categorized as Child-Pugh grade C, or death from any cause | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival， OS | overall survival (OS) was defined as the interval between the time at which treatment was initiated and death or the last follow-up assessment | 25 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Transcatheter arterial chemoembolization, Hepatic arterial infusion chemotherapy, Oxaliplatin, Raltitrexed