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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chemotherapy Effect; BCLC Stage C Hepatocellular Carcinoma
• Intervention / Treatment: Drug: intravenous FOLFOX7 plus Camrelizumab and apatinib; Drug: HAIC-FOLFOX plus Camrelizumab and apatinib

• Study Type: Interventional
• Enrollment (Estimated): 192
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yunxiuxiu Xu, MD; Phone Number: 17722864609; Email: xuyxx@mail.sysu.edu.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510000
      • Recruiting
      • Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
      • Contact: Yunxiuxiu Xu, MD; Phone Number: 17722864609; Email: xuyxx@mail.sysu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients volunteered to participate in this study and signed informed consent;
2. Age 18-75, male or female;
3. ECOG PS score 0-2;
4. Child-pugh liver function grading: Grade A or B
5. The clinical diagnosis conforms to primary hepatocellular carcinoma (HCC) and the lesion conforms to BCLC stage C
6. Did not received any type of other first-line drugs such as Sorafenib
7. 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);
8. Expected survival ≥ 12 weeks;
9. 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)
10. 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.
11. Subjects have good compliance and cooperate with the follow-up.
12. Subjects with HBV or HCV infection should receive anti-virus treatment without interfron.

Exclusion Criteria:

1. Have received immunotherapeutic drugs or interferon in the past.
2. Severe allergic reaction to other monoclonal antibodies, immunotherapy or chemotherapy.
3. Female subjects with pregnancy or on feeding.
4. Patients with congenital or acquired immune deficiencies.
5. 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
6. The patient has suffered from other malignant tumors at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ)
7. The patient has active infection, fever of unknown origin within 7 days (CTCAE>2)
8. Patients with congenital or acquired immune deficiencies.
9. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Infusional FOLFOX; Infusional mFOLFOX7 plus Camrelizumab and apatinib	Drug: intravenous FOLFOX7 plus Camrelizumab and apatinib; 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
Active Comparator: HAIC-FOLFOX; HAIC-FOLFOX plus Camrelizumab and apatinib	Drug: HAIC-FOLFOX plus Camrelizumab and apatinib; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 7, 2023
• First Posted (Estimated): December 15, 2023

Study Record Updates

• Last Update Posted (Estimated): December 15, 2023
• Last Update Submitted That Met QC Criteria: December 7, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Protective Agents; Micronutrients; Protein Kinase Inhibitors; Vitamins; Antidotes; Vitamin B Complex; Fluorouracil; Oxaliplatin; Leucovorin; Apatinib
• Other Study ID Numbers: SYSKY-2023-984-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No