Clinical Trials List
Protocol NumberKF-CSR02-001
NCT Number(ClinicalTrials.gov Identfier)NCT04601428
2020-06-01 - 2026-12-31
Phase I
Not yet recruiting1
Recruiting3
ICD-9235.3
Neoplasm of uncertain behavior of liver and biliary passage
CSR02-Fab-TF as Hepatic Intra-arterial Therapy in Intermediate Stage B or Limited Advanced Stage C Hepatocellular Carcinoma (HCC): Dose-Escalation Study to Assess Safety and Tolerability
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Trial Applicant
A2 HEALTHCARE TAIWAN CORPORATION
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Sponsor
Koo Foundation Sun Yat-Sen Cancer Center
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chien-Jui Huang Digestive System Department
- Liu Yi-Sheng Division of Radiology
- Chiu Hung Chiu Digestive System Department
- 劉奕廷 Division of Hematology & Oncology
- Hsin-Yu Kuo Digestive System Department
- 簡世杰 Digestive System Department
- Yih-Jyh Lin Division of Gastroenterological Surgery
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 蘇東弘 Division of General Internal Medicine
- Chien-Hung Chen Division of General Internal Medicine
- 楊宏志 Division of General Internal Medicine
- Sheng-chieh Chou Division of General Internal Medicine
- Chih-Hung Hsu Division of Hematology & Oncology
- Ming-Chih Ho Division of General Surgery
- 何承懋 Division of General Surgery
- Chia-Chi Lin Division of Hematology & Oncology
- Chiun Hsu Division of Hematology & Oncology
- 曾岱宗 醫學研究部
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Not yet recruiting
Condition/Disease
Intermediate stage B or limited advanced stage C hepatocellular carcinoma (HCC)
Objectives
Intra-arterial (IA) therapy is generally used to treat HCC tumors that are too extensive to excise or treat with potentially curative local therapy. IA therapy takes advantage of the fact that the blood supply of HCC comes predominantly from the hepatic artery compared with the surrounding normal liver which is predominantly supplied by portal venous blood. The intent is to deprive the HCC of its blood supply, leading to the death of the tumor. Traditionally, various methods have been used to block the HCC blood supply, but improvements are needed. This study will investigate a new agent designed in the laboratory to block only tumor blood vessels, not blood vessels in the normal liver.
Test Drug
CSR02-Fab-TF
Active Ingredient
CSR02-Fab-TF
Dosage Form
3
Dosage
mg/mL
Endpoints
Primary Outcome Measures :
Incidence and severity of adverse events from intra-arterial infusion of CSR02-Fab-TF in patients with hepatoma only or largely confined to the liver, and resistant/recurrent after prior therapy [ Time Frame: Infusion to Day 50 ]
Measured by the number of treatment-emergent adverse events and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
HCC blood flow [ Time Frame: MRI on Day 4 ]
HCC blood flow will be assessed by magnetic resonance imaging (MRI) on day 4 after infusion of CSR02-FabTF.
Secondary Outcome Measures :
Determine tumor response to intra-arterial infusion of CSR02-Fab-TF [ Time Frame: by MRI on Day 50 and then every 3 months for an average of one year. ]
Measured by radiographic response using acceptable imaging modalities used for assessment of tumor vasculature and blood flow (MRI or CT) based on mRECIST.
Incidence and severity of adverse events from intra-arterial infusion of CSR02-Fab-TF in patients with hepatoma only or largely confined to the liver, and resistant/recurrent after prior therapy [ Time Frame: Infusion to Day 50 ]
Measured by the number of treatment-emergent adverse events and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0
HCC blood flow [ Time Frame: MRI on Day 4 ]
HCC blood flow will be assessed by magnetic resonance imaging (MRI) on day 4 after infusion of CSR02-FabTF.
Secondary Outcome Measures :
Determine tumor response to intra-arterial infusion of CSR02-Fab-TF [ Time Frame: by MRI on Day 50 and then every 3 months for an average of one year. ]
Measured by radiographic response using acceptable imaging modalities used for assessment of tumor vasculature and blood flow (MRI or CT) based on mRECIST.
Inclution Criteria
Inclusion Criteria:
Age ≥ 18 years (US), Age ≥ 20 years (Taiwan)
Diagnosis of HCC by at least one of the following criteria:
Histological confirmation;
Magnetic resonance imaging (MRI) or computerized tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion > 2 cm with intense contrast uptake during the arterial phase followed by contrast washout during the venous phase regardless of alpha-fetal protein (AFP) level
Barcelona Clinic Liver Cancer (BCLC) Intermediate Stage B or limited Advanced Stage C (see Protocol Section 3.1). Patients with Stage C disease should have received or been offered and chosen not to receive systemic therapy
Inadequate response to prior liver-directed therapy (e.g., TACE, bland embolization, Y90, ablation, radiation therapy) to the same targeted area or progressive disease after prior liver-directed therapy) or to one or more systemic therapies
Not a candidate for curative resection, liver transplantation, or percutaneous ablation (See Protocol Appendix 3)
Eastern Collective Oncology Group (ECOG) performance status ≤1 (See Protocol Appendix 5)
Adequate laboratory parameters, including:
Serum total bilirubin ≤ 2.0;
Alkaline phosphatase, aspartate aminotransferase (AST) and aspartate aminotransferase (ALT) < 5 x ULN;
Serum creatinine ≤ 1.5 mg/dL;
Prothrombin time (international normalized ratio; INR) ≤ 1.5;
Absolute neutrophil count > 1000/μL;
Platelet count > 75,000/μL;
Hgb > 8 g/dL
Acceptable pulmonary status, including room air O2 saturation > 90%
Child-Pugh A-B7 without clinically significant ascites (See Protocol Appendix 4)
Signed informed consent
All subjects must be surgically sterile, at least two years post-menopausal (if female), or agree to use adequate, effective contraception approved by the Investigator until two (2) months after receiving a final dose of CSR02-Fab-TF
Age ≥ 18 years (US), Age ≥ 20 years (Taiwan)
Diagnosis of HCC by at least one of the following criteria:
Histological confirmation;
Magnetic resonance imaging (MRI) or computerized tomography (CT) consistent with liver cirrhosis AND at least one solid liver lesion > 2 cm with intense contrast uptake during the arterial phase followed by contrast washout during the venous phase regardless of alpha-fetal protein (AFP) level
Barcelona Clinic Liver Cancer (BCLC) Intermediate Stage B or limited Advanced Stage C (see Protocol Section 3.1). Patients with Stage C disease should have received or been offered and chosen not to receive systemic therapy
Inadequate response to prior liver-directed therapy (e.g., TACE, bland embolization, Y90, ablation, radiation therapy) to the same targeted area or progressive disease after prior liver-directed therapy) or to one or more systemic therapies
Not a candidate for curative resection, liver transplantation, or percutaneous ablation (See Protocol Appendix 3)
Eastern Collective Oncology Group (ECOG) performance status ≤1 (See Protocol Appendix 5)
Adequate laboratory parameters, including:
Serum total bilirubin ≤ 2.0;
Alkaline phosphatase, aspartate aminotransferase (AST) and aspartate aminotransferase (ALT) < 5 x ULN;
Serum creatinine ≤ 1.5 mg/dL;
Prothrombin time (international normalized ratio; INR) ≤ 1.5;
Absolute neutrophil count > 1000/μL;
Platelet count > 75,000/μL;
Hgb > 8 g/dL
Acceptable pulmonary status, including room air O2 saturation > 90%
Child-Pugh A-B7 without clinically significant ascites (See Protocol Appendix 4)
Signed informed consent
All subjects must be surgically sterile, at least two years post-menopausal (if female), or agree to use adequate, effective contraception approved by the Investigator until two (2) months after receiving a final dose of CSR02-Fab-TF
Exclusion Criteria
Exclusion Criteria:
Eligible for transplantation by Milan criteria (Protocol Appendix 3) or potentially eligible if successfully "down staged" by pre-transplant therapy
Prior organ transplantation
Any treatment for HCC (including TACE) or any investigational therapy within the previous 60 days or treatment with Y90 within the previous 90 days
Previously treated malignancies from which the subject has not been disease-free for at least 2 years, except for adequately treated non-melanoma skin cancer, in situ cancer, or low-grade prostate or bladder cancer
Severe chronic obstructive or other pulmonary disease with hypoxemia that requires supplementary oxygen or clinically significant pleural effusions
New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 3 months prior to therapy, unstable arrhythmia, symptomatic peripheral arterial vascular disease, or presence of an artificial or other vascular device requiring chronic anticoagulation (See Protocol Appendix 6)
Any of the following risks related to QT/QTc interval:
Baseline prolongation of QT/QTc interval (repeated interval > 480 milliseconds using Frederica's QT correction formula);
History of additional risk factors for Torsades de Pointes (e.g. heart failure, hypokalemia, family history of Long QT syndrome);
Concomitant medications that have a known risk for prolongation of the QT/QTc interval (see https://crediblemeds.org/new-drug-list/)
Major surgery, vascular injury, or serious illness within the previous 60 days
Known inherited thrombophilia (hypercoagulable state) or history of unprovoked venous thrombosis
Abnormal lupus anticoagulant
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy at screening. Subjects with prior HBV (positive HBSAg) must have HBV viral load < 500 IU/mL. Subjects with HCV infection are eligible if other eligibility criteria are met
Females who are breast-feeding
Allergy to iodinated contrast medium that is uncontrolled or refractory to medical therapy
Therapeutic anticoagulation that cannot be stopped 24-72 hours before treatment (per Section 4.3) and reinstituted no sooner than 72 hours after therapy
Any concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study
Unwillingness or inability to comply with the study protocol for any reason
Eligible for transplantation by Milan criteria (Protocol Appendix 3) or potentially eligible if successfully "down staged" by pre-transplant therapy
Prior organ transplantation
Any treatment for HCC (including TACE) or any investigational therapy within the previous 60 days or treatment with Y90 within the previous 90 days
Previously treated malignancies from which the subject has not been disease-free for at least 2 years, except for adequately treated non-melanoma skin cancer, in situ cancer, or low-grade prostate or bladder cancer
Severe chronic obstructive or other pulmonary disease with hypoxemia that requires supplementary oxygen or clinically significant pleural effusions
New York Heart Association (NYHA) Class III or IV, cardiac disease, myocardial infarction within 3 months prior to therapy, unstable arrhythmia, symptomatic peripheral arterial vascular disease, or presence of an artificial or other vascular device requiring chronic anticoagulation (See Protocol Appendix 6)
Any of the following risks related to QT/QTc interval:
Baseline prolongation of QT/QTc interval (repeated interval > 480 milliseconds using Frederica's QT correction formula);
History of additional risk factors for Torsades de Pointes (e.g. heart failure, hypokalemia, family history of Long QT syndrome);
Concomitant medications that have a known risk for prolongation of the QT/QTc interval (see https://crediblemeds.org/new-drug-list/)
Major surgery, vascular injury, or serious illness within the previous 60 days
Known inherited thrombophilia (hypercoagulable state) or history of unprovoked venous thrombosis
Abnormal lupus anticoagulant
Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy at screening. Subjects with prior HBV (positive HBSAg) must have HBV viral load < 500 IU/mL. Subjects with HCV infection are eligible if other eligibility criteria are met
Females who are breast-feeding
Allergy to iodinated contrast medium that is uncontrolled or refractory to medical therapy
Therapeutic anticoagulation that cannot be stopped 24-72 hours before treatment (per Section 4.3) and reinstituted no sooner than 72 hours after therapy
Any concomitant disease or condition that could interfere with the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the subject in this study
Unwillingness or inability to comply with the study protocol for any reason
The Estimated Number of Participants
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Taiwan
30 participants
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Global
43 participants
