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

Phase 2

• Conditions: Transarterial Chemoembolization; Hepatocellular Carcinoma
• Interventions: Drug: cTACE-HAIC

• Registration Number: NCT04597970
• Lead Sponsor: Peking University Cancer Hospital & Institute

Brief Summary

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

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：

1. Volunteer to participate and sign the informed consent in writing;

2. Age: 18-75 years old;

3. No gender limit;

4. BCLC stage C hepatocellular carcinoma with pathological diagnosis or clinical diagnosis;

5. 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.

6. At least one measurable lesion (according to mRECIST criteria) imaging diagnosis time ≤ 21 days from selection;

7. Child-pugh grade A-B7 grade

8. The expected survival period is ≥3 months;

9. ECOG Performance Status (ECOG) 0-2;

10. 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:

1. Those who are currently receiving other effective treatments;

2. Patients who have received oxaliplatin and raltitrexed in the past;

3. Patients who have participated in other clinical trials within 4 weeks before enrollment;

4. Unable to cooperate with cTACE and HAIC treatment;

5. 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;

6. 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;

7. Neurological or mental abnormalities that affect cognitive ability, including central nervous system transfer;

8. There were active serious clinical infections (\>grade 2 NCI-CTCAE version 4.0), including active tuberculosis within 14 days before enrollment;

9. Known or self-reported HIV infection;

10. Uncontrolled systemic diseases, such as poorly controlled diabetes;

11. Known to have hypersensitivity or allergic reactions to any component of the study drug;

12. 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.

Study Timeline

• Status Verified: 2020-10
• Study First Submitted: 2020-10-16
• Study First Submitted QC: 2020-10-17
• Last Update Submitted: 2020-10-17
• Study Start: 2020-10-20
• Study First Posted: 2020-10-22
• Last Update Posted: 2020-10-22
• Primary Completion: 2021-10-20
• Study Completion: 2022-10-20

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. Volunteer to participate and sign the informed consent in writing;
2. Age: 18-75 years old;
3. No gender limit;
4. BCLC stage C hepatocellular carcinoma with clear pathological diagnosis or clinical diagnosis;
5. 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.
6. At least one measurable lesion (according to mRECIST criteria) imaging diagnosis time ≤ 21 days from selection;
7. Child-pugh grade A-B7 grade
8. The expected survival period is ≥3 months;
9. General physical condition (ECOG) 0-2;
10. 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

1. Those who are currently receiving other effective treatments;
2. Patients who have received oxaliplatin and raltitrexed in the past;
3. Patients who have participated in other clinical trials within 4 weeks before enrollment;
4. Unable to cooperate with cTACE and HAIC treatment;
5. 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;
6. 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;
7. Neurological or mental abnormalities that affect cognitive ability, including central nervous system transfer;
8. There were active serious clinical infections (>grade 2 NCI-CTCAE version 4.0), including active tuberculosis within 14 days before enrollment;
9. Known or self-reported HIV infection;
10. Uncontrolled systemic diseases, such as poorly controlled diabetes;
11. Known to have hypersensitivity or allergic reactions to any component of the study drug;
12. Pregnancy (determined by serum β-chorionic gonadotropin test) or breast-feeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
cTACE-HAIC(oxaliplatin and raltitrexed)	cTACE-HAIC	Patients receive cTACE+HAIC (oxaliplatin, raltitrexed) treatment, 6-8 weeks as a cycle

Primary Outcome Measures

Name	Time	Method
Disease control rate, DCR	6 months	disease control rate (DCR) was defined as the CR rate + the PR rate + the stable disease (SD) rate
Objective response rate, ORR	6 months	The objective response rate (ORR) was defined as the complete response (CR) rate + the partial response (PR) rate
Progression free overall survival，PFS	8 months	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

Secondary Outcome Measures

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