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

March 4, 2025 updated by: Koo Foundation Sun Yat-Sen Cancer Center

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

43

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Taiwan
      • Taipei, Taiwan, 112
        • Recruiting
        • KFSYSCC
        • Contact:
        • Contact:
          • Kuo Jang (KJ) Kao, M.D., Ph.D.
    • North Dist.
      • Tainan City, North Dist., Taiwan, 70403
        • Recruiting
        • National Cheng Kung University Hospital (NCKUH)
        • Contact:
    • Pei-Tou Dist.
      • Taipei, Pei-Tou Dist., Taiwan, 11259
        • Recruiting
        • Koo Foundation Sun Yat-Sen Cancer Center (KFSYSCC)
        • Contact:
    • Zhongzheng Dist.
      • Taipei city, Zhongzheng Dist., Taiwan, 100225
        • Recruiting
        • National Taiwan University Hospital (NTUH)
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 18 years

  • 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 > 1 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 ≤ 2x ULN
    • 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 small molecule drug treatment for HCC (including TACE) within the previous 30 days, treatment with biological agents 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 or arterial thrombosis
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy at screening. Subjects with prior HBV (positive HBSAg) must have HBV viral load < 2000 IU/mL or be receiving concurrent anti-HBV therapy to be eligible. Subjects on anti-HBV therapy must have been on treatment with a viral load maintained at < 2000 IU/mL for at least 4 weeks prior to first dose and continue on this same therapy throughout study treatment. 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 4.5) 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Infusion to Day 50
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.
MRI on Day 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
by MRI on Day 50 and then every 3 months for an average of one year.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Koo Foundation Sun Yat-Sen Cancer Center

Investigators

  • Study Director: Paul Weiden, M.D., KFSYSCC consultant

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 26, 2021

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

September 29, 2020

First Submitted That Met QC Criteria

October 19, 2020

First Posted (Actual)

October 23, 2020

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 4, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KF-CSR02-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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