A Phase II Study of Cryoablation Combined with Anti-PD-1 Antibody （SHR-1210） in Patients with Advanced Intrahepatic Cholangiocarcinoma
Overview
- Phase
- Phase 2
- Intervention
- Camrelizumab
- Conditions
- Intrahepatic Cholangiocarcinoma
- Sponsor
- Fudan University
- Enrollment
- 25
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- 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 anti-pd-1 antibody in patients with advanced hepatocellular carcinoma after progression on first line systemic therapy.
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. Therefore, the objective of this study is to evaluate the efficacy and safety of cryoablation combined with anti-pd-1 antibody in patients in advanced intrahepatic cholangiocarcinoma.
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 unresectable or metastatic histologically or cytologically confirmed intrahepatic cholangiocarcinoma
- •Participants must have failed 1 line of systemic regimens for advanced cholangiocarcinoma due to disease progression or toxicity.
- •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.
- •Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment, adherence to contraceptive measures, scheduled visits and examinations including follow up.
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.
- •Radiofrequency ablation 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:
- •history of interstitial lung disease
Arms & Interventions
Cryoablation in combination with Camrelizumab
Cryoablation treatment starts at day 1. Camrelizumab will be initiated on day 14 after Cryoablation. Camrelizumab will be administered every three weeks (3mg/Kg, IV) until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention: Camrelizumab
Cryoablation in combination with Camrelizumab
Cryoablation treatment starts at day 1. Camrelizumab will be initiated on day 14 after Cryoablation. Camrelizumab will be administered every three weeks (3mg/Kg, IV) until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Intervention: US/CT-guided Percutaneous Cryoablation
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: max 24 months
Objective Response Rate according to modified RECIST for Hepatocellular Carcinoma
Secondary Outcomes
- Progression Free Survival(max 24 months)
- Duration of Response(max 24 months)
- Overall survival(max 42 months)
- disease control rate(max 24 months)
- Adverse Events(max 42 months)