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

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

Interventions

COMBINATION_PRODUCT

HAIC+PD1

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.

DRUG

HAIC

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.

Sponsors & Collaborators

• Innovent Biologics, Inc.

  collaborator OTHER

• Sun Yat-sen University

  lead OTHER

Principal Investigators

• Min-shan Chen, MD, PhD · Sun Yat-sen University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-03-25

Primary Completion

2020-07-20

Completion

2025-12-31

Countries

• China

Study Locations