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

NCT04601428 | Recruiting Early Phase 1 DMC FDA Drug

• 1 other identifier: KF-CSR02-001
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 4

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.

Conditions

Hepatocellular Carcinoma (HCC)

Keywords

Hepatocellular carcinoma; HCC; hepatoma; IA (intra-arterial) therapy; PLVAP; CSR02-Fab-TF

Outcome Measures

Primary Outcomes (2)

• 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

  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

  HCC blood flow will be assessed by magnetic resonance imaging (MRI) on day 4 after infusion of CSR02-FabTF.

  MRI on Day 4

Secondary Outcomes (1)

• Determine tumor response to intra-arterial infusion of CSR02-Fab-TF

  by MRI on Day 50 and then every 3 months for an average of one year.

Study Arms (1)

Investigational Arm

EXPERIMENTAL

Biological: IA therapy of HCC with CSR02-Fab-TF

Interventions

IA therapy of HCC with CSR02-Fab-TF BIOLOGICAL

Intra-Arterial Infusion of CSR02-Fab-TF

Investigational Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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

Sponsors & Collaborators

• Koo Foundation Sun Yat-Sen Cancer Center: lead

Study Sites (4)

National Cheng Kung University Hospital (NCKUH)

Tainan, North Dist., 70403, Taiwan

RECRUITING

Koo Foundation Sun Yat-Sen Cancer Center (KFSYSCC)

Taipei, Pei-Tou Dist., 11259, Taiwan

RECRUITING

National Taiwan University Hospital (NTUH)

Taipei, Zhongzheng Dist., 100225, Taiwan

RECRUITING

KFSYSCC

Taipei, 112, Taiwan

RECRUITING

Related Publications (2)

• Forner A, Gilabert M, Bruix J, Raoul JL. Treatment of intermediate-stage hepatocellular carcinoma. Nat Rev Clin Oncol. 2014 Sep;11(9):525-35. doi: 10.1038/nrclinonc.2014.122. Epub 2014 Aug 5.

  PMID: 25091611 BACKGROUND

• Wang YH, Cheng TY, Chen TY, Chang KM, Chuang VP, Kao KJ. Plasmalemmal Vesicle Associated Protein (PLVAP) as a therapeutic target for treatment of hepatocellular carcinoma. BMC Cancer. 2014 Nov 6;14:815. doi: 10.1186/1471-2407-14-815.

  PMID: 25376302 BACKGROUND

Related Links

• PubMed ID: 25091611 Treatment of intermediate-stage hepatocellular carcinoma
• PubMed ID: 25376302 Plasmalemmal Vesicle Associated Protein (PLVAP) as a therapeutic target for treatment of hepatocellular carcinoma

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Paul Weiden, M.D.

  KFSYSCC consultant

  STUDY DIRECTOR

Central Study Contacts

Gabriela Sanchez

CONTACT

858-630-1960; gsanchez@sciquus.com

Jennifer Schulz

CONTACT

jschulz@sciquus.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: September 29, 2020
• First Posted: October 23, 2020
• Study Start: January 26, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4)