Clinical trial NCT04220944: Combined Locoregional Treatment With Immunotherapy for Unresectable HCC.
Official title: Microwave Ablation Combined With Simultaneous TACE Plus Sintilimab for Unresectable HCC.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Hepatic Carcinoma
Keywords: HCC
Microwave ablation
TACE
Immunotherapy
Lead sponsor: Shanghai Zhongshan Hospital
Sponsor class: OTHER
Collaborators: name: Innovent Biologics (Suzhou) Co. Ltd.
First posted: 2020-01-07
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Observation period max 18 months
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: max 18 months
measure: Time to Progression (TTP)
timeFrame: max 18 months
measure: Overall survival (OS)
timeFrame: max 18 months
measure: Incidence of Treatment Emergent Adverse Events as assessed by NCI CTCAE V5.0 (Safety and Tolerability)
timeFrame: max 18 months
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Department of Interventional Radiology, Zhongshan Hospital, Fudan University.
state: Shanghai
Study officials:
affiliation: Department of Interventional Radiology, Zhongshan Hospital, Fudan University
name: zhiping Yan, MD
role: STUDY_DIRECTOR
References: