Combined Locoregional Treatment With Immunotherapy for Unresectable HCC.

Microwave Ablation Combined With Simultaneous TACE Plus Sintilimab for Unresectable HCC.

Efficacy and Safety of Locoregional treatments Combined With PD-1 Inhibitor in Patients With Unresectable Hepatocellular Carcinoma.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatic Carcinoma
• Intervention / Treatment: Drug: Sintilimab; Procedure: Microwave Ablation; Procedure: TACE

Detailed Description

Hepatocellular carcinoma is the most frequent primary and ranked as the sixth most common neoplasm and the third leading cause of cancer death.

Percutaneous ablation and TACE are the effective locoregional treatments for the patient with HCC. Moreover, some studies suggested that TACE combined with ablation could further improve the survival rate and reduce the post-operation complication.

Although PD-1 inhibitor was approved by FDA for HCC, the latest RCT indicated that no significant difference was found in the ORR and PFS between the groups of PD-1 inhibitor and Sorafenib.

Therefore, this study aims to assess the efficacy and safety of microwave ablation combined with simultaneous TACE plus PD-1 inhibitor for the non-resectable HCC.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Department of Interventional Radiology, Zhongshan Hospital, Fudan University.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: 18 - 80 years old and life expectancy of at least 12 weeks.;
2. Clinically or histologically diagnosed as HCC and the diameter of target tumor lesion ≥ 5 cm;
3. Child-pugh classification A or B (score < 7);
4. BCLC Staging as B or C;
5. ECOG 0-1;
6. Patients voluntarily entered the study and signed informed consent form (ICF).

Exclusion Criteria:

1. History of treatment with any local treatment (exception of liver transplantation), systemic .anti-cancer therapy, or immunotherapy;
2. The surgeon assessed that the tumor lesion was not unsuitable for microwave ablation;

3. Any contraindications for hepatic embolization procedures:

   1. Known hepatofugal blood flow;
   2. Total thrombosis of main portal vein.
4. The tumor thrombus of main portal vein, IVC or right atrium;
5. Tumor burden ≥ 70% of liver volume; and no measurable site of disease as defined by modified RECIST (mRECIST) criteria with spiral CT scan or MRI;
6. Subjects with chronic HBV infection have HBV DNA viral load > 100 IU/mL at screening, and have not received antiviral therapy prior to initiation of study therapy; In addition, coinfection of HBV and HCV;
7. The alcoholic or pregnant women;
8. Patients with second primary cancer or history of other cancer within 3 years;
9. Diagnosis of active autoimmune disease, immunodeficiency, or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Sintilimab-monotherapy treatment;
10. Blood count, liver function: Haemoglobin < 9.0 g/dL, white cell count < 1.0 x10^9/L; Total bilirubin > 3 mg/dL; Aspartate Aminotransferase (SGOT) or Alanine aminotransferase (SGPT) > 5 x upper normal limit (ULN), Albumin < 2.8g/dL; International normalized ratio (INR) >2.3;
11. Renal function dysfunction: Serum Creatinine >2 mg/dL or creatinine clearance (CrCl) < 30 mL/min (if using the Cockcroft-Gault formula ); and severe heart, lung, brain or other organ disease;
12. Non-compliance with TACE or ablation procedure.

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: Locoregional therapies combined with Anti-PD-1 antibody; Percutaneous microwave ablation combined with simultaneous TACE was performed. Sintilimab will be initiated on day 3-7 after the first locoregional therapies. Sintilimab will be administered every three weeks (200mg fixed dose IV) until disease progression for up to one year.The second locoregional procedure will be repeated according to the enhanced CT images.

Drug: Sintilimab; Sintilimab (200mg) was administered intravenously over 30-60 min every 3 weeks.; Other Names: Sintilimab injection, 308004; Procedure: Microwave Ablation; The ablation area should covered at least two thirds the size of the nodules.; Procedure: TACE; Patient was treated with epirubicin lipiodol emulsion(Epirubicin 40mg, Lipiodol 10ml).Embolic materials such as gelfoam or microsphere was aslo administered until complete stasis in segmental or subsegmental arterial branches.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression according to mRECIST for HCC.	Observation period max 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Objective Response Rate according to mRECIST for HCC	max 18 months
Time to Progression (TTP)	It is defined as the time from first locoregional therapy to the date of the first documented tumor progression according to the definition above.	max 18 months
Overall survival (OS)	Overall survival is defined as the time from first locoregional therapy until death	max 18 months
Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V5.0 (Safety and Tolerability)	Data will be obtained on vital signs, clinical parameters and feasibility of the regimen	max 18 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Innovent Biologics (Suzhou) Co. Ltd.
• Investigators: Study Director: zhiping Yan, MD, Department of Interventional Radiology, Zhongshan Hospital, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Estimated): October 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: December 29, 2019
• First Submitted That Met QC Criteria: January 4, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): August 1, 2024
• Last Update Submitted That Met QC Criteria: July 30, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: HCC; Immunotherapy; TACE; Microwave ablation
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma, Hepatocellular
• Other Study ID Numbers: ZS-IR-2019B

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