Back to resultsAnti-PD-1 Antibody Plus DEB-TACE for BCLC Stage A/B HCC
Primary Purpose
Hepatocellular Carcinoma
Status
Active
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Sintilimab
DEB-TACE
Sponsored by
About this trial
This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular carcinoma, Transarterial chemoembolization, Immunotherapy
Eligibility Criteria
Inclusion Criteria
- Age between 18 years and 75 years;
- ECOG PS 0/1;
- 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
- Have not received any anti-tumor systemic treatment in the past
- No contraindications for the treatment of DEB-TACE and PD-1 inhibitors;
- Liver function: Child-Pugh score Class A
- The expected survival of the patient is more than 3 months
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
- Adequate bone marrow, cardiac, and renal function
- Patients must 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.
Exclusion Criteria
- History of other malignancies；
- 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)；
- With uncontrolled hepatitis B (HBV-DNA>2000 IU/ml and elevated ALT).
- Spontaneous rupture and bleeding of HCC
- Hepatic tumor burden >50% total liver volume
- Complete occlusion of the portal vein
- Evidence of a bleeding diathesis or coagulopathy, active infections, and autoimmune disease
- Recurrent disease after surgery within the last 5 years
- History of organ transplantation or plan to have liver 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.
Sites / Locations
- the First Affiliated Hospital, Zhejiang University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
DEB-TACE+Sintilimab
Arm Description
Participants with BCLC Stage A/B Hepatocellular Carcinoma Beyond the Milan Criteria
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
Overall survival (OS)
The duration from treatment initiation to death from any cause.
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.
Objective Response Rate (ORR) per mRECIST
The proportion of complete response or partial response as optimal response among all treated patients according to mRECIST.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04174781
Brief Title
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
2. Study Status
Record Verification Date
June 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 20, 2019 (Actual)
Primary Completion Date
July 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Zhejiang University
4. Oversight
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
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular carcinoma, Transarterial chemoembolization, Immunotherapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
A Phase II Single-arm, Open-label Study
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Actual)
8. Arms, Groups, and Interventions
Arm Title
DEB-TACE+Sintilimab
Arm Type
Experimental
Arm Description
Participants with BCLC Stage A/B Hepatocellular Carcinoma Beyond the Milan Criteria
Intervention Type
Drug
Intervention Name(s)
Sintilimab
Other Intervention Name(s)
Immunotherapy, Anti-PD-1 therapy
Intervention Description
Sintilimab: 200mg iv Q3W D1
Intervention Type
Drug
Intervention Name(s)
DEB-TACE
Other Intervention Name(s)
Drug-eluting Bead Transarterial Chemoembolization
Intervention Description
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.
Primary Outcome Measure Information:
Title
Progression Free Survival (PFS) per mRECIST
Description
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).
Time Frame
36 months
Secondary Outcome Measure Information:
Title
12 mo PFS rate
Description
The percentage of patients who have not progressed or relapsed or death at the 12 mo time point since the first time of treatment.
Time Frame
36 months
Title
Overall survival (OS)
Description
The duration from treatment initiation to death from any cause.
Time Frame
36 months
Title
Pathological Response
Description
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.
Time Frame
6 months
Title
Objective Response Rate (ORR) per mRECIST
Description
The proportion of complete response or partial response as optimal response among all treated patients according to mRECIST.
Time Frame
36 months
Title
Disease Control Rate (DCR) per mRECIST
Description
The proportion of complete response, partial response or stable disease as optimal response among all treated patients according to mRECIST.
Time Frame
36 months
Title
Adverse events (AEs)
Description
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.
Time Frame
36 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Age between 18 years and 75 years;
ECOG PS 0/1;
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
Have not received any anti-tumor systemic treatment in the past
No contraindications for the treatment of DEB-TACE and PD-1 inhibitors;
Liver function: Child-Pugh score Class A
The expected survival of the patient is more than 3 months
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
Adequate bone marrow, cardiac, and renal function
Patients must 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.
Exclusion Criteria
History of other malignancies；
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)；
With uncontrolled hepatitis B (HBV-DNA>2000 IU/ml and elevated ALT).
Spontaneous rupture and bleeding of HCC
Hepatic tumor burden >50% total liver volume
Complete occlusion of the portal vein
Evidence of a bleeding diathesis or coagulopathy, active infections, and autoimmune disease
Recurrent disease after surgery within the last 5 years
History of organ transplantation or plan to have liver 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.
Facility Information:
Facility Name
the First Affiliated Hospital, Zhejiang University School of Medicine
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310009
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Anti-PD-1 Antibody Plus DEB-TACE for BCLC Stage A/B HCC
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