Clinical trial NCT04174781: Anti-PD-1 Antibody Plus DEB-TACE for BCLC Stage A/B HCC
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatocellular Carcinoma
Keywords: Hepatocellular carcinoma
Transarterial chemoembolization
Immunotherapy
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2019-11-22
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: A Phase II Single-arm, Open-label Study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Progression Free Survival (PFS) per mRECIST
timeFrame: 36 months
Secondary outcomes:
measure: 12 mo PFS rate
timeFrame: 36 months
measure: Overall survival (OS)
timeFrame: 36 months
measure: Pathological Response
timeFrame: 6 months
measure: Objective Response Rate (ORR) per mRECIST
timeFrame: 36 months
measure: Disease Control Rate (DCR) per mRECIST
timeFrame: 36 months
measure: Adverse events (AEs)
timeFrame: 36 months
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: the First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: