A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined With Tislelizumab Plus Lenvatinib as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Cryoablation
- Conditions
- Hepatocellular Carcinoma
- Sponsor
- Fudan University
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus Lenvatinib as first-line treatment in patients with advanced HCC.
Detailed Description
Recent studies have suggested that local destruction of tumor tissue by cryoablation induced activation and maturation of dendritic cells and tumor-specific T cells by cross-presentation of tumor antigens. While pd-1 blocking antibody interferes with PD-1 mediated T-cell regulatory signaling. And combination of pd-1 blocking antibody plus lenvatinib showed increased ORR in many types of human cancers. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus lenvatinib as first-line treatment in patients with advanced HCC.
Investigators
Peng Wang
Clinical Professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained.
- •Age ≥ 18 years at time of study entry.
- •Hepatocellular carcinoma confirmed by histology/cytology.
- •No systematic anti-tumor treatment has been performed.(End of postoperative adjuvant chemotherapy for more than 6 months allowed).
- •Barcelona Clinic Liver Cancer stage C. BCLC stage B, not suitable for radical surgery and/or local treatment.
- •At least one measurable site of disease as defined by RECIST v1.1 with spiral CT scan or MRI.
- •Child-Pugh: \<=7
- •Performance status (PS) ≤ 2 (ECOG scale).
- •Life expectancy of at least 12 weeks.
- •Adequate blood count, liver-enzymes, and renal function: absolute neutrophil count ≥ 1,500/L, platelets ≥75 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 )
Exclusion Criteria
- •With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma,
- •cholangiocarcinoma components in tumor tissues.
- •Have a history of hepatic encephalopathy or have a history of liver transplantation.
- •With clinical symptoms requires drainage of pleural effusion, ascites or pericardial effusion.
- •Central nervous system (CNS) metastasis.
- •History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment.
- •Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
- •Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
- •Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
- •Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
Arms & Interventions
Cryoablation combined with Tislelizumab and Lenvatinib
Cryoablation treatment starts at day 0. Tislelizumab and Lenvatinib will be initiated on day 1 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention: Cryoablation
Cryoablation combined with Tislelizumab and Lenvatinib
Cryoablation treatment starts at day 0. Tislelizumab and Lenvatinib will be initiated on day 1 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention: Tislelizumab
Cryoablation combined with Tislelizumab and Lenvatinib
Cryoablation treatment starts at day 0. Tislelizumab and Lenvatinib will be initiated on day 1 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent. Lenvatinib will be administered (bodyweight ≥ 60 kg, 12 mg; \< 60 kg, 8 mg) orally daily every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention: Lenvatinib
Outcomes
Primary Outcomes
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Time Frame: max 24 months
ORR is defined as the percentage of participants who have a confirmed complete response (CR: disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters). Responses are according to RECIST 1.1 as assessed by investigator.
Secondary Outcomes
- Progression Free Survival (PFS) evaluated by the investigator per mRECIST(max 24 months)
- Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Disease control rate (DCR) evaluated by the investigator per mRECIST(max 24 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(max 42 months)
- Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Objective Response Rate (ORR) evaluated by the investigator per HCC-specific modified Response Evaluation Criteria in Solid Tumors (mRECIST)(max 24 months)
- Overall survival (OS) evaluated by the investigator per mRECIST(max 42 months)
- Duration of Response (DOR) evaluated by the investigator per mRECIST(max 24 months)