A Phase II Study of Cryoablation Combined With Tislelizumab Plus Lenvatinib in Patients With Melanoma Liver Metastasis (CASTLE-05)
Overview
- Phase
- Phase 2
- Intervention
- Tislelizumab
- Conditions
- Melanoma
- Sponsor
- Fudan University
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- ORR
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus lenvatinib in patients with melanoma liver metastasis.
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 type of human cancers. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with Tislelizumab plus lenvatinib in patients with melanoma liver metastasis.
Investigators
Peng Wang
professor
Fudan University
Eligibility Criteria
Inclusion Criteria
- •Written informed consent obtained.
- •Age ≥ 18 years at time of study entry.
- •Participants must have melanoma liver metastasis.
- •Participants must have failed 1 line of systemic regimens due to disease progression or toxicity.
- •Participants who had received previous antiangiogenic therapy were eligible.
- •At least one measurable site of disease as defined by RECIST criteria 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
- •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.
- •RFA and resection administered less then 4 weeks prior to study treatment start.
- •Radiotherapy administered less then 4 weeks prior to study treatment start.
- •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).
- •Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
- •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:
Arms & Interventions
Cryoablation in combination with Tislelizumab plus lenvatinib
Cryoablation treatment starts at day 0. Tislelizumab plus lenvatinib will be initiated on day 14 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks plus a lenvatinib (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 in combination with Tislelizumab plus lenvatinib
Cryoablation treatment starts at day 0. Tislelizumab plus lenvatinib will be initiated on day 14 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks plus a lenvatinib (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 in combination with Tislelizumab plus lenvatinib
Cryoablation treatment starts at day 0. Tislelizumab plus lenvatinib will be initiated on day 14 after cryoablation. Tislelizumab will be administered at 200 mg i.v. every 3 weeks plus a lenvatinib (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
ORR
Time Frame: max 24 months
Objective Response Rate according to RECIST 1.1
Secondary Outcomes
- TTR(max 24 months)
- DoR(max 24 months)
- Adverse Events(max 24 months)
- DCR(max 24 months)
- PFS(max 24 months)
- OS(max 24 months)