Combined Locoregional Treatment With Immunotherapy for Unresectable HCC.

• ClinicalTrials.gov Identifier: NCT04220944
• Recruitment Status: Unknown
• First Posted: January 7, 2020
• Last Update Posted: September 24, 2021
• Sponsor: Shanghai Zhongshan Hospital
• Collaborator: Innovent Biologics (Suzhou) Co. Ltd.
• Information provided by (Responsible Party): Shanghai Zhongshan Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hepatic Carcinoma	Drug: Sintilimab; Procedure: Microwave Ablation; Procedure: TACE	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Microwave Ablation Combined With Simultaneous TACE Plus Sintilimab for Unresectable HCC.
• Actual Study Start Date: January 1, 2020
• Estimated Primary Completion Date: June 30, 2022
• Estimated Study Completion Date: September 30, 2022

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

1. Progression Free Survival (PFS) [ Time Frame: Observation period max 18 months ]
   Progression according to mRECIST for HCC.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: zhiping Yan, MD; +8613681971205; yan.zhiping@zs-hospital.sh.cn

Contact: minjie Yang, MD; +8613818947653; yang.minjie@zs-hospital.sh.cn

Locations

China, Shanghai

Department of Interventional Radiology, Zhongshan Hospital, Fudan University.; Recruiting

Shanghai, Shanghai, China, 200032

Contact: minjie Yang, MD +8613818947653 yang.minjie@zs-hospital.sh.cn

Sponsors and Collaborators

Shanghai Zhongshan Hospital

Innovent Biologics (Suzhou) Co. Ltd.

Investigators

• Study Director: zhiping Yan, MD; Department of Interventional Radiology, Zhongshan Hospital, Fudan University

More Information

• Responsible Party: Shanghai Zhongshan Hospital
• ClinicalTrials.gov Identifier: NCT04220944
• Other Study ID Numbers: ZS-IR-2019B
• First Posted: January 7, 2020
• Last Update Posted: September 24, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Shanghai Zhongshan Hospital:

HCC; Microwave ablation; TACE; Immunotherapy

Additional relevant MeSH terms:

Carcinoma, Hepatocellular; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases