FOLFOX Chemotherapy Plus Fruquintinib and Sintilimab After First-line Treatment in Unresectable Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

— FOLFOX  

Official title:

FOLFOX Chemotherapy (Oxaliplatin, Fluorouracil, and Leucovorin), Fruquintinib and Sintilimab After First-line Treatment in Patients With Unresectable Hepatocellular Carcinoma: A Single-arm, Single-center, Phase II Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06446154
• Other study ID #: FOLFRUS-001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2024
• Est. completion date: July 1, 2026

Study information

• Verified date: June 2024
• Source: Sun Yat-sen University
• Contact: Ming Shi
• Phone: 020-87343115
• Email: shiming[@]sysu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Nowadays, there are few second-line treatment options for advanced hepatocellular carcinoma (HCC). In order to further improve the efficacy of second-line treatment for advanced HCC, we plan to conduct a single-arm, single-center and phase II clinical study to explore the efficacy and safety of the new second-line treatment for advanced HCC.

Previous studies had shown that FOLFOX systemic chemotherapy tended to increase the median survival time of patients with advanced HCC, and significantly improved the progression-free survival and tumor response rate. Therefore, FOLFOX systemic chemotherapy has become one of the recommended treatments for advanced HCC in Chinese guidelines.

A phase II clinical study had showed that sintilimab combined with fruquintinib was with a promising anti-tumor activity in patients with advanced HCC who had received standard treatment, with a median progression-free survival of 7.4 months and a tumor response rate of 31.6%. Furthermore, there was a synergistic effect among chemotherapy, immunotherapy and anti-angiogenic therapy. Our previous phase II study showed that the median progression-free survival was 9.73 months, the median overall survival time was 14.63 months, and the tumor response rate was 43.3% in HCC patients extrahepatic metastasis who received FOLFOX systemic chemotherapy combined with targeted and immunotherapy. The results from our study suggested that the combination therapy had excellent anti-tumor efficacy and safety profile.

Therefore. We intend to conduct this clinical study to explore the efficacy and safety of FOLFOX systemic chemotherapy combined with fruquintinib and sintilimab in second-line treatment for patients with unresectable HCC after first-line treatment.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 36
• Est. completion date: July 1, 2026
• Est. primary completion date: December 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• patients aged 18 years or older

• with unresectable, locally advanced, or metastatic HCC, with the diagnosis confirmed by histologic or cytologic analysis or clinical features according to the American Association for the Study of Liver Disease criteria

• who had received previously atezolizumab/sintilimab plus bevacizumab, lenvatinib, sorafenib or camrelizumab plus rivoceranib

• had at least on measurable disease, as defined by Response Evaluation Criteria In Solid Tumours version 1.1 (RECIST v1.1) criteria

• had a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

• had a Child-Pugh liver function score of 7 or less

• had adequate hematologic and organ function (absolute neutrophil count =1.2×109/l, platelet count =60×109/l, total bilirubin < 30µmol/l, albumin = 30g/l, aspartate transaminase and alanine transaminase = 5×upper limit of the normal, creatinine clearance rate of = 1.5×upper limit of the normal, and left ventricular ejection = 45%)

Exclusion Criteria:

• history of HIV, organ allograft

• combined with other malignant tumors

• evidence of hepatic decompensation, bleeding diathesis or event

• allergy to the investigational agents or any agent given in association with this trial

• incomplete medical information.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma
• Immunotherapy
• Second-line Treatment

Intervention

Drug:
• FOLFOX systemic chemotherapy plus fruquintinib and sintilimab
The current PICC catheterization was unified for patients undergoing FOLFOX systemic chemotherapy. After catheterization, the catheter was connected to the injection pump in the ward and was continuously pumped into the following chemotherapeutic drugs. The chemotherapy was repeated every 3 weeks for a total of 8 courses. Oxaliplatin, 85mg/m2,IV (intra venous),Day 1. Calcium folinate, 400mg/m2,IV,Day1. 5FU, 400mg/m2, IV, Day1, sequentially 2400mg/m2, IV, lasting for 46 hours. Fruquintinib was given orally for 5mg/ days. After 3 weeks, the drug was stopped for 1 week. Sintilimab was infused intravenously 200mg each time, repeated every three weeks.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR	Objective response rate	Two years
Secondary	OS	Median overall survival	Two years
Secondary	PFS	Median progression-free survival	Two years