Combining hepatic arterial infusion with Apatinib and Camrelizumab for advanced liver cancer treatment

A Randomized Controlled, Open-label, Multicenter Phase III Clinical Trial to Evaluate the Effectiveness and Safety of Hepatic Arterial Infusion Chemotherapy (HAIC) of Oxaliplatin, 5-fluorouracil and Leucovorin (mFOLFOX7) Combined With Apatinib and Camrelizumab Versus Apatinib and Camrelizumab for C-staged Hepatocellular Carcinoma in BCLC Classification.

This study is testing if combining a special chemotherapy method with two drugs, Apatinib and Camrelizumab, can help people with advanced liver cancer live longer and feel better compared to just using the two drugs alone.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: Camrelizumab, apatinib, immunotherapy, prednisone, chemotherapy
• Locations: 5 sites (Guangzhou, Guangdong and 4 other locations)
• Trial ID: NCT05313282 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness and safety of combining hepatic arterial infusion chemotherapy with Apatinib and Camrelizumab compared to Apatinib and Camrelizumab alone for patients with C-staged Hepatocellular Carcinoma. The study aims to measure progression-free survival as the primary outcome, alongside secondary outcomes such as overall survival, time to progression, and safety assessments. The trial targets patients with advanced liver cancer who are not suitable for surgery or local therapies, focusing on improving treatment responses and survival rates.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with unresectable BCLC C-stage hepatocellular carcinoma and no prior systemic therapy.

Not a fit: Patients with prior systemic therapy or those with Child-Pugh scores greater than 6 may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment approach could significantly improve survival outcomes for patients with advanced liver cancer.

How similar studies have performed: Previous studies have shown promising results with similar combination therapies, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. The patient voluntarily joins the study and signs an informed consent;
2. Age ≥ 18 years old,both men and women;
3. Clinical or pathologically confirmed unresectable BCLC C-stage hepatocellular carcinoma according to AASLD: HCC with vascular invasion and/or extrahepatic metastasis which is not suitable for radical surgery and/or local therapy, or progressed after surgery and/or local therapy
4. No prior systemic therapy;
5. At least one intrahepatic evaluable tumor existed according to RECIST 1.1;
6. Child-Pugh score small or equal to 6 points ;
7. Patient can swallow tablet normally;
8. ECOG score: 0 to 1 (according to the ECOG score classification);
9. The expected survival is longer than 12 weeks;
10. The laboratory parameters meets the following requirements (no blood components and cell growth factors are allowed within 14 days before the first dose):

    * Absolute neutrophil count ≥ 3.0 × 10\^9 / L;
    * Platelets ≥ 80 × 10\^9 / L;
    * Hemoglobin ≥ 90 g / L;
    * serum albumin ≥ 28 g / L;
    * Thyroid stimulating hormone (TSH) ≤ 1 × ULN (if abnormalities should be considered at the same time FT3, FT4 levels, patients with FT3 and FT4 levels in normal range can also be enrolled);
    * bilirubin ≤ 1.5 × ULN (within 7 days prior to the first dose);
    * ALT ≤ 3 x ULN and AST ≤ 3 x ULN (within 7 days prior to the first dose);
    * AKP ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN;
11. Patients with active hepatitis B virus (HBV) infection recieve anti-HBV therapy at the screening stage and are willing to receive antiviral therapy throughout the study period; hepatitis C virus (HCV) ribonucleic acid (RNA)-positive patients must receive antiviral therapy according to local standard treatment guidelines;
12. For female that non-surgical sterilization or in childbearing age need to use a medically approved contraceptive (such as an intrauterine device, contraceptive or condom) during the study period and within 3 months after the end of the study treatment period; For female that non-surgical sterilization or in childbearing age must have a negative serum or urine HCG test within 72 hours prior to study enrollment; and must be non-lactating; for male patients whose partner in a childbearing age, effective methods of contraception should be given during the trial and at the end of Camrelizumab injection.

Exclusion Criteria:

1. The patient has any active auto-immune disease or a history of auto-immune disease (such as the following, but not limited to: auto-immune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, nephritis, thyroid hyperfunction; patients with vitiligo. For patient with history of asthma, complete remission of asthma in childhood without any intervention after adulthood can be included, while those asthma patients who require bronchodilators for medical intervention cannot be included.);
2. The patient is using immunosuppressive agents or systemic hormonal therapy for immunosuppression purposes (dose \> 10 mg/day of prednisone or other therapeutic hormones) and continues to be used within 2 weeks prior to enrollment;
3. Severe allergic reactions to other monoclonal antibodies;
4. Known for a history of central nervous system metastasis or hepatic encephalopathy;
5. Having a history of organ transplantation;
6. Patients with clinically symptomatic ascites who require puncture, drainage, or ascites drainage within 3 months, except for those who have a small amount of ascites but no clinical symptoms;
7. Suffering from hypertension, and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥90 mmHg);
8. Suffering heart diseases with clinical symptoms or those not well controlled, such as: (1) heart failure in NYHA class 2 or higher; (2) unstable angina; (3) myocardial infarction occurred within 1 year; (4) clinically symptomatic supraventricular or ventricular arrhythmia requiring treatment or intervention; (5) Tc \> 450ms (male); QTc \> 470ms (female);
9. Coagulation dysfunction (INR\>2.0, PT\>16s), bleeding tendency or receiving thrombolysis or anticoagulant therapy, allowing prophylactic use of low-dose aspirin or low molecular heparin;
10. There are significant clinically significant bleeding symptoms or clear bleeding tendency within 3 months before enrollment, such as hemoptysis of 2.5ml or more per day, gastrointestinal bleeding, esophageal varices with bleeding risk, hemorrhagic gastric ulcer or vasculitis, etc. If the fecal occult blood is positive in the baseline period, it can be watched, then gastroscope is needed for those fecal occult blood is still positive. If the gastroscope indicates severe esophageal varices, it cannot be enrolled, except for those who have undergone gastroscopy within a month or less to exclude such cases);
11. Events of arterial/venous thrombosis occurring within the first 6 months of enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, cerebral infarction), deep vein thrombosis, and pulmonary embolism;
12. There are known hereditary or acquired bleeding and thrombophilia (such as hemophilia patients, coagulopathy, thrombocytopenia, etc.);
13. Urine routine indicates that urine protein ≥ ++ and 24-hour urine protein amount \> 1.0g was confirmed;
14. The patient has active infection, unexplained fever (≥38.5 °C) within 3 days before administration, or baseline white blood cell count\>15×109/L; 15 Patients with congenital or acquired immunodeficiency (such as HIV-infected patients);

16. HBV-DNA\>2000 IU/ml (or 104 copies/ml); or HCV-RNA\>103 copies/ml; or HBsAg+ and anti-HCV antibody positive patients; 17. The patient has had other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ); 18. Patients with bone metastases who had received palliative radiotherapy \>4% of the bone marrow area within 4 weeks prior to participation in the study; 19. Patients have previously received other anti-PD-1 antibody therapy or other immunotherapy against PD-1/PD-L1, or have received apatinib before; 20. Inoculation of a live vaccine within less than 4 weeks prior to study or possibly during the study period; 21. Pregnant or lactating women, or women of childbearing age who are unwilling to take contraceptive measures; 22. According to the investigators, the patient has other factors that may affect the results of the study or lead to the termination of the study, such as alcohol abuse, drug abuse, other serious diseases (including mental illness) requiring combined treatment, and serious laboratory tests, abnormalities, accompanied by factors such as family or society, which may affect the safety of enrolled patients.

Where this trial is running

Guangzhou, Guangdong and 4 other locations

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Recruiting)
• Sun Yat-Sen Memorial Hospital — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Nanfang Hospital of Southern Medical University — Guangzhou, Guangdong, China (Not_yet_recruiting)
• The Third Affiliated Hospital of Sun Yat-Sen University — Guanzhou, Guangdong, China (Not_yet_recruiting)
• Xiangya Hospital of Central South University — Changsha, Hunan, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Yang-kui Gu, Prof.

Conditions C-staged Hepatocellular Carcinoma in BCLC Classification; C-staged Hepatocellular Carcinoma; hepatic arterial infusion chemotherapy; anti-PD-1 immunotherapy; Camrelizumab; anti-angiogenic targeted therapy; Apatinib