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A Study Evaluating Cadonilimab Injection in Combination With Regorafenib for the Advanced Hepatocellular Carcinoma

Primary Purpose

Advanced Hepatocellular Carcinoma That Has Failed at Least One Prior Systemic Therapy

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Cadonilimab Injection
Regorafenib
Sponsored by
Tianjin Medical University Cancer Institute and Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Advanced Hepatocellular Carcinoma That Has Failed at Least One Prior Systemic Therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: written informed consent signed prior to enrolment. age > 18 years, both sexes patients with histologically or pathologically confirmed intermediate to advanced hepatocellular carcinoma. intermediate to advanced HCC previously treated with anti-PD-1/PD-L1 combined with anti-vascular targeting agents for HCC, with disease progression. Child-Pugh A or B. with measurable lesions (≥10 mm long diameter on CT scan for non-lymph node lesions and ≥15 mm short diameter on CT scan for lymph node lesions according to RECIST 1.1 criteria). ECOG PS score: 0 to 1. expected survival of >12 weeks. function of vital organs in accordance with the following requirements (excluding the use of any blood components and cell growth factors within 14 days). 1) Blood count. Neutrophils ≥ 1.5 x 109/L Platelet count ≥ 60×109/L haemoglobin ≥ 90 g/L. 2) Liver and kidney function. Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula). total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN) Glutamic aminotransferase (AST) or glutamic aminotransferase (ALT) levels ≤ 10 times the upper limit of normal (ULN); urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification must show ≤ 1 g of protein. 10. normal coagulation function, no active bleeding or thrombotic disease International normalised ratio INR ≤ 1.5 x ULN. partial thromboplastin time APTT ≤ 1.5 x ULN. prothrombin time PT ≤ 1.5 x ULN. 11. Female patients who are non-surgically sterilised or of childbearing age are required to use a medically approved contraceptive (e.g. IUD, pill or condom) during and for 3 months after the end of the study treatment period; female patients of childbearing age who are non-surgically sterilised must have a negative serum or urine HCG test within 7 days prior to study entry; and must be non-lactating; male patients who are non-surgically sterilised or of childbearing age Patients, need to agree to use a medically approved form of contraception with their spouse during and for 3 months after the end of the study treatment period. 12. The subject is voluntarily enrolled in the study, is compliant and cooperates with safety and survival follow-up Exclusion criteria: Exclusion criteria Patients with any of the following are not eligible for enrollment in this study. Subjects with previous or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix). the subject has received previous immunotherapy other than anti-PD-1/PD-L1 monoclonal antibody; the subject is known to have a previous allergy to macromolecular protein agents, or is known to be allergic to the components of the drug applied. The subject has any active autoimmune disease or history of autoimmune disease (e.g. the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, previous thyroid surgery cannot be included; the subject has vitiligo or has complete remission of asthma in childhood and in adulthood (subjects who do not require any intervention can be included; subjects with asthma requiring medical intervention with bronchodilators cannot be included). subjects who are on immunosuppressive, or systemic, or absorbable topical hormone therapy for immunosuppressive purposes (doses >10 mg/day of prednisone or other isotonic hormones) and who continue to use them within 2 weeks prior to enrolment have clinically symptomatic ascites or pleural effusion requiring therapeutic puncture or requiring frequent drainage of ascites (≥1 time/month) subjects with clinically symptomatic cardiac conditions or diseases that are not well controlled, such as (1) NYHA class 2 or higher heart failure (2) unstable angina pectoris (3) previous myocardial infarction within 1 year (4) patients with clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention subjects with active infection or unexplained fever >38.5 degrees during screening and prior to the first dose (subjects with fever arising from a tumour may be enrolled, as judged by the investigator) patients with previous and current objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severely impaired lung function subjects with congenital or acquired immune deficiency, e.g. HIV infection subjects who have received a live vaccine less than 4 weeks prior to study drug administration or possibly during the study period subjects with a known history of psychotropic substance abuse, alcoholism or drug use patients who are unable to administer the drug orally have received herbal or proprietary Chinese medicine with an anti-tumour indication within 2 weeks prior to the first dose . 14 Patients who, in the opinion of the investigator, should be excluded from the study, for example, subjects who, in the judgment of the investigator, have other factors that may force the study to be terminated, e.g., other serious illnesses (including psychiatric illnesses) requiring comorbid treatment, severe fundic esophageal varices, serious laboratory test abnormalities, accompanying family or social factors that would compromise the safety of the subject, or the collection of data and samples.

Sites / Locations

  • Tianjin Cancer Hospital Airport HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Cadonilimab Injection in combination with Regorafenib

Arm Description

Cadonilimab Injection in combination with Regorafenib

Outcomes

Primary Outcome Measures

Overall response rate ( ORR)
Defined as proportion of patients who have a best response of CR or PR
Overall survival (OS)
OS is defined as the time from date of neoadjuvant treatment start to the date of death from any cause or to the date of last follow-up if patients are alive. If a patient is alive by the time of final analysis, the patient will be censored at the last follow-up date.
Progress Free Survival (PFS)
Defined as the time from enrollment to disease progression or death (whichever occurs first)
Adverse Events (AEs)
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0

Secondary Outcome Measures

Full Information

First Posted
November 30, 2022
Last Updated
December 7, 2022
Sponsor
Tianjin Medical University Cancer Institute and Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT05644379
Brief Title
A Study Evaluating Cadonilimab Injection in Combination With Regorafenib for the Advanced Hepatocellular Carcinoma
Official Title
An Open, Single-arm, Single-centre Clinical Study Evaluating Cadonilimab Injection in Combination With Regorafenib for the Treatment of Intermediate to Advanced Hepatocellular Carcinoma That Has Failed at Least One Prior Systemic Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 25, 2022 (Actual)
Primary Completion Date
November 2025 (Anticipated)
Study Completion Date
November 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Tianjin Medical University Cancer Institute and Hospital

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
To evaluate the efficacy and safety of Cadonilimab Injection in combination with Regorafenib in the treatment of intermediate to advanced hepatocellular carcinoma that has failed at least one prior systemic therapy .
Detailed Description
An open, single-arm, single-centre clinical study evaluating Cadonilimab Injection in combination with Regorafenib for the treatment of intermediate to advanced hepatocellular carcinoma that has failed at least one prior systemic therapy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Advanced Hepatocellular Carcinoma That Has Failed at Least One Prior Systemic Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cadonilimab Injection in combination with Regorafenib
Arm Type
Experimental
Arm Description
Cadonilimab Injection in combination with Regorafenib
Intervention Type
Drug
Intervention Name(s)
Cadonilimab Injection
Other Intervention Name(s)
AK104
Intervention Description
Cadonilimab Injection, 6mg/kg, intravenous drip ,q2w,
Intervention Type
Drug
Intervention Name(s)
Regorafenib
Intervention Description
Regorafenib 80mg, po, orally once daily
Primary Outcome Measure Information:
Title
Overall response rate ( ORR)
Description
Defined as proportion of patients who have a best response of CR or PR
Time Frame
up to 1 years
Title
Overall survival (OS)
Description
OS is defined as the time from date of neoadjuvant treatment start to the date of death from any cause or to the date of last follow-up if patients are alive. If a patient is alive by the time of final analysis, the patient will be censored at the last follow-up date.
Time Frame
up to 3 years
Title
Progress Free Survival (PFS)
Description
Defined as the time from enrollment to disease progression or death (whichever occurs first)
Time Frame
up to 3 years
Title
Adverse Events (AEs)
Description
Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0
Time Frame
up to 3 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: written informed consent signed prior to enrolment. age > 18 years, both sexes patients with histologically or pathologically confirmed intermediate to advanced hepatocellular carcinoma. intermediate to advanced HCC previously treated with anti-PD-1/PD-L1 combined with anti-vascular targeting agents for HCC, with disease progression. Child-Pugh A or B. with measurable lesions (≥10 mm long diameter on CT scan for non-lymph node lesions and ≥15 mm short diameter on CT scan for lymph node lesions according to RECIST 1.1 criteria). ECOG PS score: 0 to 1. expected survival of >12 weeks. function of vital organs in accordance with the following requirements (excluding the use of any blood components and cell growth factors within 14 days). 1) Blood count. Neutrophils ≥ 1.5 x 109/L Platelet count ≥ 60×109/L haemoglobin ≥ 90 g/L. 2) Liver and kidney function. Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula). total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN) Glutamic aminotransferase (AST) or glutamic aminotransferase (ALT) levels ≤ 10 times the upper limit of normal (ULN); urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification must show ≤ 1 g of protein. 10. normal coagulation function, no active bleeding or thrombotic disease International normalised ratio INR ≤ 1.5 x ULN. partial thromboplastin time APTT ≤ 1.5 x ULN. prothrombin time PT ≤ 1.5 x ULN. 11. Female patients who are non-surgically sterilised or of childbearing age are required to use a medically approved contraceptive (e.g. IUD, pill or condom) during and for 3 months after the end of the study treatment period; female patients of childbearing age who are non-surgically sterilised must have a negative serum or urine HCG test within 7 days prior to study entry; and must be non-lactating; male patients who are non-surgically sterilised or of childbearing age Patients, need to agree to use a medically approved form of contraception with their spouse during and for 3 months after the end of the study treatment period. 12. The subject is voluntarily enrolled in the study, is compliant and cooperates with safety and survival follow-up Exclusion criteria: Exclusion criteria Patients with any of the following are not eligible for enrollment in this study. Subjects with previous or concurrent other malignancies (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix). the subject has received previous immunotherapy other than anti-PD-1/PD-L1 monoclonal antibody; the subject is known to have a previous allergy to macromolecular protein agents, or is known to be allergic to the components of the drug applied. The subject has any active autoimmune disease or history of autoimmune disease (e.g. the following, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism, previous thyroid surgery cannot be included; the subject has vitiligo or has complete remission of asthma in childhood and in adulthood (subjects who do not require any intervention can be included; subjects with asthma requiring medical intervention with bronchodilators cannot be included). subjects who are on immunosuppressive, or systemic, or absorbable topical hormone therapy for immunosuppressive purposes (doses >10 mg/day of prednisone or other isotonic hormones) and who continue to use them within 2 weeks prior to enrolment have clinically symptomatic ascites or pleural effusion requiring therapeutic puncture or requiring frequent drainage of ascites (≥1 time/month) subjects with clinically symptomatic cardiac conditions or diseases that are not well controlled, such as (1) NYHA class 2 or higher heart failure (2) unstable angina pectoris (3) previous myocardial infarction within 1 year (4) patients with clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention subjects with active infection or unexplained fever >38.5 degrees during screening and prior to the first dose (subjects with fever arising from a tumour may be enrolled, as judged by the investigator) patients with previous and current objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, or severely impaired lung function subjects with congenital or acquired immune deficiency, e.g. HIV infection subjects who have received a live vaccine less than 4 weeks prior to study drug administration or possibly during the study period subjects with a known history of psychotropic substance abuse, alcoholism or drug use patients who are unable to administer the drug orally have received herbal or proprietary Chinese medicine with an anti-tumour indication within 2 weeks prior to the first dose . 14 Patients who, in the opinion of the investigator, should be excluded from the study, for example, subjects who, in the judgment of the investigator, have other factors that may force the study to be terminated, e.g., other serious illnesses (including psychiatric illnesses) requiring comorbid treatment, severe fundic esophageal varices, serious laboratory test abnormalities, accompanying family or social factors that would compromise the safety of the subject, or the collection of data and samples.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Huikai Li, MD
Phone
18622228639
Email
tjchlhk@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Yayue Liu, Doctor
Phone
18822002320
Facility Information:
Facility Name
Tianjin Cancer Hospital Airport Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300308
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Huikai Li, MD
Phone
18622228639
Email
tjchlhk@126.com
First Name & Middle Initial & Last Name & Degree
Yayue Liu, Doctor
Phone
18822002320

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Study Evaluating Cadonilimab Injection in Combination With Regorafenib for the Advanced Hepatocellular Carcinoma

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