Clinical Trials /

ET140203 T-Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma

NCT04634357

Description:

Open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety/tolerability and preliminary efficacy of ET140203 T-cells in pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB, HCN-NOS, or HCC.

Related Conditions:
  • Hepatoblastoma
  • Hepatocellular Carcinoma
  • Liver Neoplasm
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: ET140203 T-Cells in Pediatric Subjects With Hepatoblastoma, HCN-NOS, or Hepatocellular Carcinoma
  • Official Title: An Open-Label, Dose Escalation, Phase I/II Clinical Trial of ET140203 T-Cells in Pediatric Subjects With Relapsed/Refractory Hepatoblastoma (HB), Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS), or Hepatocellular Carcinoma (HCC)

Clinical Trial IDs

  • ORG STUDY ID: ETUS20AFPAR123
  • NCT ID: NCT04634357

Conditions

  • Hepatoblastoma
  • Hepatocellular Carcinoma (HCC)
  • Liver Neoplasms
  • Metastatic Liver Cancer
  • Liver Cancer
  • HEMNOS

Interventions

DrugSynonymsArms
ET140203 T CellsET140203 T-Cells

Purpose

Open-label, dose escalation, multi-center, Phase I/II clinical trial to assess the safety/tolerability and preliminary efficacy of ET140203 T-cells in pediatric subjects who are AFP-positive/HLA-A2-positive and have relapsed/refractory HB, HCN-NOS, or HCC.

Detailed Description

      The trial starts with a dose escalation phase. A traditional dose escalation model (3+3)
      design will be used to determine the recommended phase II dose (RP2D). Subjects will then be
      treated at the RP2D in the expansion phase of the trial.

      Following treatment, tumor response assessments will be performed at Months 1, 3, 6, 9, 12,
      18, and 24. At each tumor response assessment visit, imaging will be performed (triphasic CT
      Scan) and used for response evaluation. Serum AFP levels will also be measured at each tumor
      response assessment visit.

      The active assessment phase of the study will continue for 2 years. Subjects will be followed
      for 15 years post-treatment for assessment of treatment safety and overall survival.
    

Trial Arms

NameTypeDescriptionInterventions
ET140203 T-CellsExperimentalET140203 T-Cells
  • ET140203 T Cells

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed HB, HCN-NOS, or HCC with serum AFP >200ng/ml at the time of
             screening and following the most recent line of therapy.

          2. Disease reoccurrence after remission following initial standard-of-care (SOC)
             treatment (i.e. relapse) or failure of response to SOC treatment (i.e. refractory).

          3. Age ≥ 1 year and ≤ 21 years.

          4. Molecular Human Leukocyte Antigen (HLA) class I allele typing that confirms subject
             carries at least one HLA-A2 allele.

          5. Life expectancy of > 4 months per Principal Investigator's opinion.

          6. Lansky or Karnofsky Performance Scale ≥ 70.

          7. For enrollment to the dose-finding cohort, subjects must have at least one (1) lesion
             ≥ 5 mm in diameter or two (2) or more lesions ≥ 3 mm in diameter. For the
             dose-expansion cohort, subjects must have measurable disease by RECIST v1.1.

          8. Child-Pugh score of B7 or better.

          9. Adequate organ function as defined below:

               -  Serum creatinine within normal range for age/gender or a glomerular filtration
                  rate (GFR) ≥ 60 mL/min/1.73m2 for subjects with creatinine levels above
                  institutional normal.

               -  Total serum bilirubin ≤ 2 times upper limit of normal (ULN), alanine
                  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 times ULN.

               -  Left ventricular ejection fraction (LVEF) measured by echocardiogram (ECHO) > 45%
                  (evaluation performed within-6 weeks of screening does not need to be repeated).

               -  Diffusing capacity of the lung for carbon monoxide (DLCO) and forced expiratory
                  volume in one (1) second (FEV1) > 45% predicted. If unable to perform pulmonary
                  function tests due to age, no evidence of dyspnea at rest and a pulse oximetry >
                  94%.

               -  Absolute neutrophil count (ANC) ≥ 750/mm3 (109/L).

        Exclusion Criteria:

          1. Pre-existing illness including ongoing or active infection (see below), heart failure,
             uncontrolled pulmonary disease not cancer-related, or psychiatric illness/social
             situation that would limit compliance with study requirements.

             Guidelines for Hepatitis B and C:

               -  Hepatitis B: Exclude subjects with viral load >20,000 IU/mL (>105 copies/mL).

               -  Hepatitis C: Exclude subjects who have not demonstrated negative PCR for 6 months
                  after treatment.

          2. Any known active malignancy (other than HB, HCN-NOS, or HCC).

          3. Pregnant or lactating women.

          4. Received the following within two (2) weeks of leukapheresis and within two (2) weeks
             of conditioning chemotherapy: cytotoxic chemotherapy, radiation, systemic
             corticosteroids, other anti-cancer therapies (including immunotherapeutic agents), or
             any other immunosuppressive agents (Note: use of inhaled or topical steroids is not
             exclusionary).

          5. Concurrently receiving other investigational agents, biological, chemical, or
             radiation therapies, while participating in the study.

          6. Contraindication for receipt of conditioning chemotherapeutic agents including
             Fludarabine and Cyclophosphamide.

          7. Active autoimmune disease requiring systemic immunosuppressive therapy.

          8. Compromised circulation in the main portal vein, hepatic vein, or vena cava due to
             partial or complete obstruction which, in the opinion of the Principal Investigator,
             would make the subject unsuitable for the study.

          9. History of organ transplant.

         10. HB, HCN-NOS, or HCC involving greater than 50% of the liver (volumetric).
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence rates of adverse events (AEs) after infusion of ET140203 T cells
Time Frame:28 days
Safety Issue:
Description:Safety of ET140203 T cells as assessed by the number of adverse events (AEs) after infusion

Secondary Outcome Measures

Measure:Assess the efficacy of ET140203 T cells in pediatric subjects with relapsed/refractory HB, HCN-NOS, or HCC
Time Frame:Up to 2 years
Safety Issue:
Description:Response rate will be assessed by radiographic scans and assessed according to RECIST criteria.
Measure:Determine the pharmacokinetics of ET140203 T cells after infusion.
Time Frame:Up to 2 years
Safety Issue:
Description:Assess the expansion and persistence of ET140203 T cells circulating in blood over time.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Eureka Therapeutics Inc.

Trial Keywords

  • Relapsed/Refractory Hepatoblastoma (HB)
  • Pediatric
  • Hepatocellular Neoplasm-Not Otherwise Specified (HCN-NOS)
  • Hepatocellular Carcinoma (HCC)
  • Liver Cancer
  • T-cell therapy
  • Metastatic Liver Cancer
  • Liver neoplasms
  • HEMNOS

Last Updated

November 18, 2020