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Cryoablation Combined With Tislelizumab Plus Lenvatinib in 1L Treatment of Advanced HCC (CASTLE-10) (CASTLE-10)

Primary Purpose

Hepatocellular Carcinoma

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
Cryoablation
Tislelizumab
Lenvatinib
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 ) 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: With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, 1. 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). 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) known acute or chronic pancreatitis active tuberculosis any other active infection (viral, fungal or bacterial) requiring systemic therapy history of allogeneic tissue/solid organ transplant 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 Tislelizumab treatment. 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. i) Live vaccine within 30 days prior to the first dose of Tislelizumab treatment or during study treatment. j) 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.

Sites / Locations

  • Fudan University Shanghai Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cryoablation combined with Tislelizumab and Lenvatinib

Arm Description

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.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
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 Outcome Measures

Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)
Objective Response Rate (ORR) evaluated by the investigator per HCC-specific modified Response Evaluation Criteria in Solid Tumors (mRECIST)
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 mRECIST as assessed by investigator.
Progression Free Survival (PFS) evaluated by the investigator per mRECIST
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
Overall survival (OS) evaluated by the investigator per mRECIST
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death
Duration of Response (DOR) evaluated by the investigator per mRECIST
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Disease control rate (DCR) evaluated by the investigator per mRECIST
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.

Full Information

First Posted
May 31, 2023
Last Updated
June 24, 2023
Sponsor
Fudan University
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1. Study Identification

Unique Protocol Identification Number
NCT05897268
Brief Title
Cryoablation Combined With Tislelizumab Plus Lenvatinib in 1L Treatment of Advanced HCC (CASTLE-10)
Acronym
CASTLE-10
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 20, 2023 (Actual)
Primary Completion Date
December 30, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cryoablation combined with Tislelizumab and Lenvatinib
Arm Type
Experimental
Arm Description
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 Type
Procedure
Intervention Name(s)
Cryoablation
Intervention Description
Cryoablation is performed under US or CT guidance per Investigator decision.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
a PD-1 immune check inhibitor
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Intervention Description
Lenvatinib capsules
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Description
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.
Time Frame
max 24 months
Secondary Outcome Measure Information:
Title
Progression Free Survival (PFS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Description
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
Time Frame
max 24 months
Title
Overall survival (OS) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Description
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death
Time Frame
max 24 months
Title
Duration of Response (DOR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Description
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Time Frame
max 24 months
Title
Disease control rate (DCR) evaluated by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1
Description
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)
Time Frame
max 24 months
Title
Objective Response Rate (ORR) evaluated by the investigator per HCC-specific modified Response Evaluation Criteria in Solid Tumors (mRECIST)
Description
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 mRECIST as assessed by investigator.
Time Frame
max 24 months
Title
Progression Free Survival (PFS) evaluated by the investigator per mRECIST
Description
PFS is defined as the time from study treatment to disease progression or all-cause death as assessed by the investigator (whichever occurs first)
Time Frame
max 24 months
Title
Overall survival (OS) evaluated by the investigator per mRECIST
Description
OS is defined as the time from study treatment to the date of death of the subject, regardless of the cause of death
Time Frame
max 42 months
Title
Duration of Response (DOR) evaluated by the investigator per mRECIST
Description
DOR is defined as the time from first documented complete or partial response until disease progression, death from any cause, or censoring at date of last tumor assessment.
Time Frame
max 24 months
Title
Disease control rate (DCR) evaluated by the investigator per mRECIST
Description
DCR is defined as the proportion of patients with complete response (CR), partial response (PR) and stable disease (SD)
Time Frame
max 24 months
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Description
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The percentage of participants who experience at least one AE will be reported.
Time Frame
max 42 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 ) 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: With fibrous lamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, 1. 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). 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) known acute or chronic pancreatitis active tuberculosis any other active infection (viral, fungal or bacterial) requiring systemic therapy history of allogeneic tissue/solid organ transplant 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 Tislelizumab treatment. 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. i) Live vaccine within 30 days prior to the first dose of Tislelizumab treatment or during study treatment. j) 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peng Wang, MD
Phone
86-21-64175590
Email
wangp413@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Peng Wang, MD
Phone
86-21-64175590
Email
peng_wang@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peng Wang, MD
Organizational Affiliation
Fudan University Shanghai Cancer Center, Shanghai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peng Wang, M.D.
Phone
862164175590
Ext
83630
Email
peng_wang@fudan.edu.cn

12. IPD Sharing Statement

Learn more about this trial

Cryoablation Combined With Tislelizumab Plus Lenvatinib in 1L Treatment of Advanced HCC (CASTLE-10)

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