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Hepatic IA Therapy in Stage B or Limited Stage C Hepatoma (HCC)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04601428
Recruitment Status : Recruiting
First Posted : October 23, 2020
Last Update Posted : March 16, 2023
Information provided by (Responsible Party):
Koo Foundation Sun Yat-Sen Cancer Center

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Hepatocellular Carcinoma (HCC) Biological: IA therapy of HCC with CSR02-Fab-TF Early Phase 1

Detailed Description:
Genetic testing was done to identify differences between HCC tumors and normal liver, and a protein, PLVAP, was shown to be present on the blood vessels of HCC but not on the blood vessels of normal liver. An antibody, CSR02, was made that recognizes PLVAP and then the Fab portion of that antibody was combined with tissue factor, a normal human protein that initiates the clotting cascade. The result is a manufactured (recombinant) protein called CSR02-Fab-TF. Preclinical studies in a mouse model showed that infusion of an equivalent mouse protein resulted in the necrosis (death) of a transplanted human HCC. The current study is designed first, to identify a safe and optimal dose of CSR02-Fab-TF in patients , and then second, to determine the response rate of HCC tumors to the IA administration of CSR02-Fab-TF.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: The dose escalation phase of the study will begin with 3 single cohort subjects and then proceed to a traditional 3 +3 study design until a Maximum Tolerated Dose (MTD) or an active dose (i.e., a dose at which subjects achieve a complete response in the liver or complete elimination of tumor blood flow) is identified. Once an appropriate dose in established, an expansion phase will administer CSR02-Fab-TF to 16 additional subjects to estimate the response proportion in subjects with refractory HCC.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 26, 2021
Estimated Primary Completion Date : December 2023
Estimated Study Completion Date : December 2023

Arm Intervention/treatment
Experimental: Investigational Arm Biological: IA therapy of HCC with CSR02-Fab-TF
Intra-Arterial Infusion of CSR02-Fab-TF

Primary Outcome Measures :
  1. 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

  2. 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 :
  1. 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.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04601428

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Contact: Gabriela Sanchez 858-630-1960
Contact: Jennifer Schulz

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United States, Maryland
University of Maryland Recruiting
Baltimore, Maryland, United States, 21201
Contact: Dr. Kevin Kim    410-328-3477   
United States, Missouri
Washington University School of Medicine, Mallinckrodt Institute of Radiology Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Robin Haverman    314-747-1624   
United States, Texas
UT Southwestern Medical Center Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Kelli Keys   
United States, Washington
University of Washington Recruiting
Seattle, Washington, United States, 98115
Contact: Madilyn Heit    206-727-1077   
National Cheng Kung University Hospital (NCKUH) Recruiting
Tainan City, North Dist., Taiwan, 70403
Contact: Meng-Yun Kuo    +886-919-013-926   
Koo Foundation Sun Yat-Sen Cancer Center (KFSYSCC) Recruiting
Taipei, Pei-Tou Dist., Taiwan, 11259
Contact: Ya-Chen Pan    +886-2-2897-0011 ext 1671   
National Taiwan University Hospital (NTUH) Recruiting
Taipei city, Zhongzheng Dist., Taiwan, 100225
Contact: Yun-Ping Lin    +886-905-705-570   
KFSYSCC Recruiting
Taipei, Taiwan, 112
Contact: Kuo Jang (KJ) Kao, M.D., Ph.D.    886-2-2897-0011 ext 3316   
Principal Investigator: Kuo Jang (KJ) Kao, M.D., Ph.D.         
Sponsors and Collaborators
Koo Foundation Sun Yat-Sen Cancer Center
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Study Director: Paul Weiden, M.D. KFSYSCC consultant
Study Director: Joseph Purvis, M.D. Linical Americas
Additional Information:
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Responsible Party: Koo Foundation Sun Yat-Sen Cancer Center Identifier: NCT04601428    
Other Study ID Numbers: KF-CSR02-001
First Posted: October 23, 2020    Key Record Dates
Last Update Posted: March 16, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Koo Foundation Sun Yat-Sen Cancer Center:
Hepatocellular carcinoma
IA (intra-arterial) therapy
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases