Anti-PD-1 Antibody Plus DEB-TACE for BCLC Stage A/B HCC

Preoperative Anti-PD-1 Antibody Plus Drug-eluting Bead TACE for BCLC Stage A/B Hepatocellular Carcinoma Beyond the Milan Criteria: A Phase II Trial

This study aimed to evaluate the efficacy and the safety of the anti-programmed-death-1 antibody (anti-PD-1) Sintilimab Injection in combination with transarterial chemoembolization with drug-eluting beads(TACE-DEB) in patients with BCLC Stage A/B Hepatocellular Carcinoma Beyond the Milan Criteria.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Sintilimab; Drug: DEB-TACE

Detailed Description

Patients with hepatocellular carcinoma (HCC) of BCLC stage A/B exceeding the Milan criteria have a low resection rate and high postoperative recurrence rate, therefore, optimizing therapy for these patients is an important unmet need. This study aimed to investigate the efficacy and safety of preoperative DEB-TACE plus sintilimab for the treatment of patients with BCLC stage A/B HCC exceeding the Milan criteria.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The First Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

1. Age between 18 years and 75 years;
2. ECOG PS 0/1;
3. Patients with histologically- or clinically-confirmed HCC (based on the American Association for the Study of Liver Diseases criteria) that was either BCLC stage A and exceeded the Milan criteria, or BCLC stage B
4. Have not received any anti-tumor systemic treatment in the past
5. No contraindications for the treatment of DEB-TACE and PD-1 inhibitors;
6. Liver function: Child-Pugh score Class A
7. The expected survival of the patient is more than 3 months

8. The following conditions must be met:

   Platelets ≥ 75 × 10^9/L White blood cell count (WBC) ≥ 3.0 × 10^9/L Hemoglobin ≥ 90 g/L Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); total bilirubin (TBIL) ≤ 1.5 × ULN Blood creatinine ≤ 1.5 × ULN PT prolonged ≤ 3 s

9. Adequate bone marrow, cardiac, and renal function
10. Patients must agree to accept postoperative follow-up required by the design of this study;
11. 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.

Exclusion Criteria

1. History of other malignancies；
2. 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 5.0 adverse events of grade 2)；
3. With uncontrolled hepatitis B (HBV-DNA>2000 IU/ml and elevated ALT).
4. Spontaneous rupture and bleeding of HCC
5. Hepatic tumor burden >50% total liver volume
6. Complete occlusion of the portal vein
7. Evidence of a bleeding diathesis or coagulopathy, active infections, and autoimmune disease
8. Recurrent disease after surgery within the last 5 years
9. History of organ transplantation or plan to have liver transplantation;
10. Pregnant women, nursing mothers.
11. Patients have other factors that may interfere with patient enrollment and assessment results.
12. Refuse follow-up as required by this study protocol and refuse to sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: DEB-TACE+Sintilimab; Participants with BCLC Stage A/B Hepatocellular Carcinoma Beyond the Milan Criteria

Drug: Sintilimab; Sintilimab: 200mg iv Q3W D1; Other Names: Immunotherapy; Anti-PD-1 therapy; Drug: DEB-TACE; DEB-TACE(epirubicin 60mg) D1; Additional DEB-TACE procedures were carried out every 4-6 weeks based on tumor response. A treatment cycle was defined as one DEB-TACE procedure plus two doses of sintilimab. The combination of DEB-TACE and sintilimab was continued for a maximum of 3 cycles until surgical resection, radiologic disease progression, unacceptable toxicity, or withdrawal from the study, whichever occurred first.; Other Names: Drug-eluting Bead Transarterial Chemoembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) per mRECIST	The duration from treatment initiation to PD in patients who cannot undergo surgery, or to the date of postoperative relapse in patients who receive surgery, or death for any reason, whichever occurs first (according to mRECIST).	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12 mo PFS rate	The percentage of patients who have not progressed or relapsed or death at the 12 mo time point since the first time of treatment.	36 months
Overall survival (OS)	The duration from treatment initiation to death from any cause.	36 months
Pathological Response	Including Major Pathological response rate（MPR）and pathological complete response (pCR). MPR is defined as the presence of 10% or fewer viable tumour cells in the primary tumours. pCR is defined as no viable tumour cells in the specimen.	6 months
Objective Response Rate (ORR) per mRECIST	The proportion of complete response or partial response as optimal response among all treated patients according to mRECIST.	36 months
Disease Control Rate (DCR) per mRECIST	The proportion of complete response, partial response or stable disease as optimal response among all treated patients according to mRECIST.	36 months
Adverse events (AEs)	The incidence, relationship with study drugs, and severity level of all adverse events (AEs) according to CTCAE 5.0, treatment-emergent adverse events (TEAEs), treatment related adverse events (TRAEs), and serious adverse events (SAEs) and the changes in vital signs, physical examination results, and laboratory test results before, during, and after the treatment.	36 months

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Anticipated): July 30, 2022
• Study Completion (Anticipated): December 30, 2022

Study Registration Dates

• First Submitted: November 20, 2019
• First Submitted That Met QC Criteria: November 20, 2019
• First Posted (Actual): November 22, 2019

Study Record Updates

• Last Update Posted (Actual): June 9, 2022
• Last Update Submitted That Met QC Criteria: June 6, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Immunotherapy; Hepatocellular carcinoma; Transarterial chemoembolization
• 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
• Other Study ID Numbers: CISLD-5

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
• product manufactured in and exported from the U.S.: No