Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)

Trial Title: Cryoablation Combined With Sintilimab Plus Lenvatinib in 1L Treatment of Advanced ICC (CASTLE-ICC-Chemo-free)

NCT ID: NCT05835245

Condition: Advanced Intrahepatic Cholangiocarcinoma

Conditions: Official terms:
Cholangiocarcinoma
Lenvatinib

Study type: Interventional

Study phase: Phase 2

Overall status: Recruiting

Study design:

Allocation: N/A

Intervention model: Single Group Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Procedure
Intervention name: Cryoablation
Description: Cryoablation is performed under US or CT guidance per Investigator decision.
Arm group label: Cryoablation combined with Sintilimab and Lenvatinib

Intervention type: Drug
Intervention name: Sintilimab
Description: a PD-1 immune check inhibitor
Arm group label: Cryoablation combined with Sintilimab and Lenvatinib

Intervention type: Drug
Intervention name: Lenvatinib
Description: Lenvatinib capsules
Arm group label: Cryoablation combined with Sintilimab and Lenvatinib

Summary: The objective of this study is to evaluate the efficacy and safety of cryoablation combined with Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.

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 Sintilimab plus lenvatinib as first-line treatment in patients with advanced ICC.

Criteria for eligibility:
Criteria:
Inclusion Criteria: - Written informed consent obtained. - Age ≥ 18 years at time of study entry. - Advanced ICC with diagnosis confirmed by histology or cytology. - Patients with no prior systemic chemotherapy or targeted therapy or loco-regional therapy (including but not limited to transarterial chemoembolization, transarterial embolization, transarterial chemotherapy or transarterial radioembolization) or immunotherapy for ICC. Patients with recurrent disease more than 6 months after completion of adjuvant chemotherapy following curative resection are 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. - 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: - Diagnosis of hepatocellular carcinoma (HCC), mixed cholangiocarcinoma and HCC, sarcomatoid hepatocellular carcinoma, or hepatic fibrolamellar carcinoma by histology or cytology. - 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: 1. history of interstitial lung disease 2. Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection) 3. known acute or chronic pancreatitis 4. active tuberculosis 5. any other active infection (viral, fungal or bacterial) requiring systemic therapy 6. history of allogeneic tissue/solid organ transplant 7. diagnosis of 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 treatment. 8. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study. 9. Live vaccine within 30 days prior to the first dose of Sintilimab treatment or during study treatment. 10. History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of Tislelizumab treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS - Medication that is known to interfere with any of the agents applied in the trial. - Any other efficacious cancer treatment except protocol specified treatment at study start. - Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening. - Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Fudan University Shanghai Cancer Center

Address:
City: Shanghai
Zip: 200032
Country: China

Status: Recruiting

Contact:
Last name: Peng Wang, M.D.

Phone: 862164175590

Phone ext: 83630
Email: peng_wang@fudan.edu.cn

Start date: April 28, 2023

Completion date: December 30, 2025

Lead sponsor:
Agency: Fudan University
Agency class: Other

Source: Fudan University

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT05835245