cTACE Plus Sintilimab for Unresectable Intermediate-stage HCC With Beyond Up-to-seven Criteria

NCT04842565 | Completed Phase 2

• 1 other identifier: B2020-178R
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the efficacy and safety of Sintilimab plus Transcatheter arterial chemoembolization (TACE) in participants with Intermediate-stage unresectable hepatocellular carcinoma with Beyond Up-to-seven Criteria.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-free survival time (mPFS) (mRECIST)

  The progression-free survival time (mPFS) is defined as the date from the first TACE to the date of first documented disease progression as assessed by mRECIST or death.

  Up to approximately 24 months

Secondary Outcomes (5)

• Overall Survival (OS)

  Up to approximately 24 months

• Percentage of Participants With Adverse Events

  Up to approximately 24 months

• Objective response rate (ORR) by RECIST 1.1 and mRECIST

  Up to approximately 24 months

• Progression-free survival time (mPFS) (RECICL)

  Up to approximately 24 months

• Time to Progression (TTP)

  Up to approximately 24 months

Study Arms (1)

TACE+Sintilimab

EXPERIMENTAL

Drug: Sintilimab; Device: TACE

Interventions

Sintilimab DRUG

Sintilimab (200mg ivdrip D1 Q3W)

TACE+Sintilimab

TACE DEVICE

TACE will be performed by clinical demand, the interval between two TACEs is not less than 4 weeks.

TACE+Sintilimab

Eligibility Criteria

• Age: 20 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥20 and ≤75 years old
• Clinically diagnosed or pathologically confirmed advanced hepatocellular carcinoma. ( Fibrolamellae and mixed hepatocellular/cholangiocarcinoma subtypes are not included)
• CNLC stage IIa/IIb or BCLC stage B, not eligible for resection or local ablation, beyond up-to-seven criteria (hepatocellular carcinomas with seven as the sum of the size of the largest tumor \[in cm\] and the number of tumors)
• Newly diagnosed or recurrent more than half a year after radical surgery
• No prior TACE treatment,
• Child-Pugh A, ECOG PS: 0-1
• Patients with chronic HBV infection must have HBV DNA viral load \< 500 IU/mL at screening. In addition, they must be on antiviral therapy per regional standard of care guidelines prior to initiation of study therapy.
• At least one measurable site of disease as defined by modified RECIST (mRECIST) and RECICL criteria with spiral CT scan or MRI.
• Life expectancy of at least 3 months.
• Adequate blood count, liver-enzymes, and renal function: Haemoglobin ≥ 8.5 g/dL, absolute neutrophil count ≥ 1,500/L, platelets ≥70 x103/L; Total bilirubin ≤ 3x upper normal limit; Aspartate Aminotransferase (SGOT), Alanine aminotransferase (SGPT) ≤ 5 x upper normal limit (ULN); International normalized ratio (INR) ≤1.25; Albumin ≥ 31 g/dL; Serum Creatinine ≤ 1.5 x institutional ULN or creatinine clearance (CrCl) ≥ 30 mL/min (if using the Cockcroft-Gault formula )
• Patients are willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.
• Normal T3 and T4. (T3 and T4 controlled in the normal range through treatment is also eligible.)
• Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.

You may not qualify if:

• Diffuse HCC or presence of vascular invasion or extrahepatic spread.
• The patient suffered from other malignant tumors in the past 3 years or at the same time (except for cured skin basal cell carcinoma and cervical carcinoma in situ).
• Known history of hepatic encephalopathy within 6 months
• Known history of cardiac disease within 12 months before the first dose of study drug.
• Clinically significant hemoptysis or tumor bleeding of any reason within 2 weeks before the first dose of study drug.
• Severe unhealed wounds, ulcers, or fractures
• Prior systemic anti-cancer therapy.
• Prior treatment with TACE.
• Suffer from high blood pressure and cannot be well controlled by antihypertensive drugs (systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)
• Any active autoimmune disease or a history of autoimmune disease.
• Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
• History of allogeneic tissue/solid organ transplant.
• Urine routine test showed urine protein ≥ ++ and confirmed 24-hour urine protein content\> 1.0 g.
• Prior therapy with an anti-Programmed cell death protein 1 (anti-PD-1), anti-PD-L1, anti-Programmed cell death-ligand 2 (anti-PD-L2), anti-CD137 (4-1BB ligand, a member of the Tumor Necrosis Factor Receptor (TNFR) family), or anti-Cytotoxic T-lymphocyte-associated antigen-4 (anti-CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Female patients who are pregnant, breast-feeding.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Zhongshan Hospital

Shanghai, Shanghai Municipality, 200032, China

Location

Related Publications (1)

• Li L, Xu X, Wang W, Huang P, Yu L, Ren Z, Fan J, Zhou J, Zhang L, Wang Z. Safety and efficacy of PD-1 inhibitor (sintilimab) combined with transarterial chemoembolization as the initial treatment in patients with intermediate-stage hepatocellular carcinoma beyond up-to-seven criteria. J Immunother Cancer. 2025 Jan 16;13(1):e010035. doi: 10.1136/jitc-2024-010035.

  PMID: 39824532 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 Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor

Study Record Dates

• First Submitted: April 8, 2021
• First Posted: April 13, 2021
• Study Start: May 1, 2021
• Primary Completion: May 1, 2022
• Study Completion: May 1, 2023
• Last Updated: May 22, 2024

Record last verified: 2024-05

Locations

CN (1)