HAIC Combined with PD-1 Inhibitor in Potentially Resectable Locally Advanced HCC

NCT03869034 | Active Not Recruiting Phase 2

• 1 other identifier: HAICPD1-HCC
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Hepatocellular carcinoma patients are mostly diagnosed at locally advanced stage. Nowadays, hepatic artery interventional therapy and/or systemic therapy are the main treatments options for these patients. Our previous study showed that compared to than conventional transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC) has better objective response, better safety profile, and increased resection rates. The PD-1 inhibitors emerged in recent years have shown good momentum in the treatment of hepatocellular carcinoma. The single-drug treatment on advanced hepatocellular carcinoma has a tumor response rate of 17%, the disease control rate exceeds 60%, and the overall survival time exceeds 12 months. And it has good tolerance and less adverse events. In studies of other cancer, combined with traditional chemotherapy can further improve the efficacy of PD-1 inhibitors. Our study is a prospective phase II clinical study for patients with potentially resectable locally advanced hepatocellular carcinoma (tumor confined to the liver with invasion to branches of the portal vein or hepatic vein). Progressive survival (PFS) is the primary end point of study. The OS and overall survival rate, RFS, ORR, DCR, conversion rate, pathological response, and safety are the secondary endpoints. The efficacy and safety of HAIC combined with PD-1 inhibitor in the treatment of potentially resectable locally advanced hepatocellular carcinoma will be discussed.

Conditions

Hepatocellular Carcinoma

Keywords

Hepatic arterial Infusion Chemotherapy; PD-1 Inhibitor; Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS) assessed by RECIST 1.1

  The duration from treatment initiation to disease progression or death from any cause in patients who did not undergo surgery, or to the date of postoperative relapse or death from any cause in patients who had received surgery, whichever occurs first. The baseline of the tumor before the initial treatment was used as a reference, and the assessments are performed according to the RECIST 1.1 criteria based on the imaging test (enhanced CT or MRI).

  From date of the first treatment until the date of progression or death from any cause, whichever occurs first, assessed up to 96 months

Secondary Outcomes (8)

• Overall survival (OS)

  From date of the first treatment until the date of death from any cause, assessed up to 96 months

• 1-, 2- and 3-year Overall Survival (OS) rate

  From date of the first treatment until the date of death from any cause, assessed up to 96 months

• Safety: the percentage of participants with treatment-related adverse events as assessed by CTCAE v4.03

  From date of the first treamtment until 100 days after the last treatment.

• Pathological Response: pathological complete response (pCR) and major pathological response (MPR: >90% of tumor necrosis)

  Through study completion, an average of 1 year.

• Objective Response Rate (ORR) assessed by RECIST 1.1

  Through study completion, an average of 3 year.

Other Outcomes (1)

• Biomarkers of treatment response by single-cell RNA sequencing

  From date of first dose until the date of first documented progression, assessed up to 96 months

Study Arms (2)

A, Combination group (HAIC+PD-1)

EXPERIMENTAL

HAIC+PD-1

Combination Product: HAIC+PD1

B, HAIC group (HAIC only)

EXPERIMENTAL

HAIC

Drug: HAIC

Interventions

HAIC+PD1 COMBINATION_PRODUCT

Sintilimab ( 200mg Q3W iv D1)+FOLFOX-HAIC（oxaliplatin, 130 mg/m2 and leucovorin, 200 mg/m2, and fluorouracil, 400 mg/m2, bolus and 2400 mg/m2 over 46 hours Q3W D2 D3), maximally 8 cycles Multi-disciplinary consultation was organized to decide the chance of surgery and subsequent treatment per 2 treatment cycles. Patients who achieved partial response (PR) or minor response (MR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and were assessed as eligible for R0 resection go on to undergo surgical resection. After recovery from operation , sintilimab monotherapy was given per three weeks for maximally 16 doses. Patients who were ineligible for resection would continue to receive the combination therapy.

Also known as: Sintilimab (IBI308), FOLFOX-HAIC

A, Combination group (HAIC+PD-1)

HAIC DRUG

FOLFOX-HAIC: oxaliplatin, 130 mg/m2 and leucovorin, 200 mg/m2, and fluorouracil, 400 mg/m2, bolus and 2400 mg/m2 over 46 hours Q3W D2 D3, for maximally 8 cycles, and the safety parameters are reviewed before the start of each course of HAIC treatment. Patients who achieve partial response (PR) or minor response (MR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and are assessed as eligible for R0 resection go on to undergo surgical resection. No other anti-tumor therapies are allowed before PD or postoperative relapse is confirmed.

Also known as: FOLFOX-HAIC

B, HAIC group (HAIC only)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 years and 70 years.
• Hepatocellular carcinoma: patients need to be diagnosed as hepatocellular carcinoma (HCC) histologically before treatment.
• Never received any anti-cancer treatment in the past.
• potentially resectable Locally advanced HCC: with at least one measurable lesion (RECIST 1.1), and tumor(s) confined to the left or right hemi-liver, with macroscopic invasion to branch of the portal vein and/or hepatic vein.
• No extrahepatic metastases.
• No contraindications for the treatment of HAIC and PD-1 inhibitors.
• KPS≥90.
• Liver function: Child-Pugh class A.
• The expected survival of the patient is more than 6 months.
• Adequate hematological and organ function.
• The following conditions are met:
• Platelet≥75×10\^9/L; White blood cell≥3.0×10\^9/L; Hemoglobin≥90 g/L; Serum creatinine≤1.5 × upper limit of normal (ULN); PT≤3 second extension; total bilirubin ≤1.5 x ULN； AST and ALT ≤2.5 x ULN.
• Agree to accept postoperative follow-up required by the design of this study.
• Patients must have the ability to understand and voluntarily sign the informed consent, and must sign an informed consent before starting any specific procedure for the study.

You may not qualify if:

• In combined with severe heart, lung, kidney or other important organ dysfunction, or combined with serious infection or other serious associated diseases, that cannot tolerate treatment (\> CTCAE Version 4.03 adverse events of grade 2).
• With uncontrolled hepatitis B (HBV-DNA\>2000 IU/ml and elevated ALT).
• Multi-nodules hepatocellular carcinoma beyond hemi-hepatic range.
• Patients with tumor thrombus reaches or exceeds the portal vein.
• History of other malignancies.
• History of allergic reactions to related drugs.
• History of organ transplantation.
• Pregnant women, nursing mothers.
• Patients have other factors that may interfere with patient enrollment and assessment results.
• Refuse follow-up as required by this study protocol and refuse to sign informed consent.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Innovent Biologics, Inc.: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

Related Publications (4)

• Lyu N, Kong Y, Mu L, Lin Y, Li J, Liu Y, Zhang Z, Zheng L, Deng H, Li S, Xie Q, Guo R, Shi M, Xu L, Cai X, Wu P, Zhao M. Hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin vs. sorafenib for advanced hepatocellular carcinoma. J Hepatol. 2018 Jul;69(1):60-69. doi: 10.1016/j.jhep.2018.02.008. Epub 2018 Feb 20.

  PMID: 29471013 BACKGROUND

• Lyu N, Lin Y, Kong Y, Zhang Z, Liu L, Zheng L, Mu L, Wang J, Li X, Pan T, Xie Q, Liu Y, Lin A, Wu P, Zhao M. FOXAI: a phase II trial evaluating the efficacy and safety of hepatic arterial infusion of oxaliplatin plus fluorouracil/leucovorin for advanced hepatocellular carcinoma. Gut. 2018 Feb;67(2):395-396. doi: 10.1136/gutjnl-2017-314138. Epub 2017 Jun 7. No abstract available.

  PMID: 28592441 BACKGROUND

• He MK, Le Y, Li QJ, Yu ZS, Li SH, Wei W, Guo RP, Shi M. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study. Chin J Cancer. 2017 Oct 23;36(1):83. doi: 10.1186/s40880-017-0251-2.

  PMID: 29061175 BACKGROUND

• Pan Y, Wang X, Peng C, Zhao J, Lu S, Zhang C, Wang J, Fu Y, Zhou Z, Chen M, Zhang Y, Xu L. Hepatic arterial infusion chemotherapy plus sintilimab as conversion therapy for locally advanced hepatocellular carcinoma: a single-center phase II trial. Int J Surg. 2026 Jan 13. doi: 10.1097/JS9.0000000000004692. Online ahead of print.

  PMID: 41537370 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

sintilimab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Min-shan Chen, MD, PhD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None in this study will be masked.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Model Details: Patients enroll in this study will receive hepatic arterial infusion chemotherapy with FOLFOX regimen (FOLFOX-HAIC), or combined with Sintilimab PD-1 inhibitor.

Study Record Dates

• First Submitted: March 2, 2019
• First Posted: March 11, 2019
• Study Start: March 25, 2019
• Primary Completion: July 20, 2020
• Study Completion: December 31, 2025
• Last Updated: December 3, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: since publication
• Access Criteria: open

Locations

CN (1)