A Phase II Study to Evaluate the Efficacy and Safety of Cryoablation Combined with Tislelizumab Plus Lenvatinib in Previously Treated Solid Tumors
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab
- Conditions
- Solid Tumor, Adult
- 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
- last year
Overview
Brief Summary
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus Lenvatinib for patients with previously treated solid tumors.
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 in previously treated solid tumors.
Investigators
Peng Wang
Clinical Professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained.
- •Age ≥ 18 years at time of study entry.
- •Participants must have solid tumors.
- •Participants must have failed from chemotherapy or other anti-cancer therapy or standard therapy was no longer feasible.
- •Participants who had received previous anti-angiogenesis or anti-PD1/PDL1 therapy were eligible.
- •At least one measurable site of disease as defined by RECIST v1.1 with spiral CT scan or MRI.
- •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 )
- •Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.
Exclusion Criteria
- •Uncontrolled pericardial effusion, pleural effusion, or clinically significant moderate or severe ascites that is symptomatic or requires thoracentesis or paracentesis during the screening phase for control of symptoms.
- •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.
- •Prior treatment with cryoablation.
- •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).
- •Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to:
- •history of interstitial lung disease
- •Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
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: 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
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
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
- Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1(max 24 months)
- Number of participants with treatment-related adverse events as assessed by CTCAE v5.0(max 42 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)