Clinical Trials /

A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR

NCT02687386

Description:

This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours.

Related Conditions:
  • Diffuse Intrinsic Pontine Glioma
  • Malignant Central Nervous System Neoplasm
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR
  • Official Title: A Phase 1 Study of Intravenous EGFR-ErbituxEDVsMIT (EEDVsMit) in Children With Recurrent / Refractory Solid or CNS Tumours Expressing Epidermal Growth Factor Receptor (EGFR) (ECREST Study)

Clinical Trial IDs

  • ORG STUDY ID: KCA001
  • NCT ID: NCT02687386

Conditions

  • Solid Tumours
  • CNS Tumours

Interventions

DrugSynonymsArms
Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)EDV also stands for EnGeneIC Dream VectorMitoxantrone packaged EDV

Purpose

This is an open-label, sequential dose exploration study of single agent EEDVSMit administered by intravenous (IV) infusion twice weekly, followed by weekly maintenance dosing, in children with recurrent/refractory solid or CNS tumours.

Detailed Description

      Eligible subjects enrolled in the study will receive EEDVSMit by IV injection twice weekly as
      a 20 min infusion beginning at study day 1 for the first cycle (4 weeks) then weekly for
      subsequent cycles. Subjects will undergo radiological assessment of their tumours after the
      first cycle, and every second cycle thereafter. Dosing with EEDVSmit will continue unless
      there is radiographic evidence of progressive disease (PD) per RECIST criteria version 1.1,
      the subject becomes intolerant to the study medication, signs and symptoms of clinical
      progression are evident as determined by the principal investigator, or the
      subject/parent/guardian withdraws consent. Suspected tumour progression should be confirmed
      with a repeat scan after 4 weeks to exclude the possibility of pseudoprogression.

      Determination of EGFR expression for eligibility of subjects will be assessed at the local
      site. In addition, radiological assessment confirming measurable disease by the RECIST
      criteria is also required for entry into the Part B of the study.

      The study will be conducted in two parts: Part A -Dose Exploration and Part B -Dose
      Expansion.

      Part A - Dose Exploration:

      The dose exploration part of the study is aimed at determining a recommended phase 2 dose
      (RP2D) in this patient group. A standard dose escalation with a rolling 6 design will be
      used.

      Part A will commence dosing at one log scale below the maximum dose tested in the recent
      adult recurrent glioma trial (with the first 4 doses administered at 1/10 of the starting
      dose) and escalate to a maximum of 8x109 EEDVSMit evaluating the safety and tolerability, of
      EEDVSMit. The first 4 doses administered will be reduced by a further log reduction.

      Part B - Dose expansion:

      The dose expansion phase (Part B) will begin upon completion of the dose exploration (Part
      A). Up to 12 subjects with recurrent/refractory solid or CNS tumours will be treated at the
      Recommended Phase Two Dose (RPTD). All doses, including the first 4, will be at the same dose
      level established in Part A (RPTD).
    

Trial Arms

NameTypeDescriptionInterventions
Mitoxantrone packaged EDVExperimentalMitoxantrone packaged EDV (EnGeneIC Dream Vector)
  • Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)

Eligibility Criteria

        Inclusion Criteria:

          -  Patients must be ≥ 2 years and ≤ 21 years old at the time of study enrolment.

          -  Karnofsky ≥ 50% for patients > 16 years of age and Lansky ≥ 50 for patients ≤ 16 years
             of age

          -  Patients must have relapsed or refractory solid or CNS tumours or have a diagnosis of
             DIPG. Patients must have had histologic verification of malignancy at original
             diagnosis or relapse, or a diagnosis of DIPG by MRI imaging.

          -  Patients must have either measurable or evaluable disease for Part B of the study only

          -  Patient's current disease state must be one for which there is no known curative
             therapy or therapy proven to prolong survival with an acceptable quality of life.

          -  Patients must have fully recovered from the acute toxic effects of all prior
             chemotherapy, immunotherapy, or radiotherapy prior to entering this study

        Exclusion Criteria:

          -  Pregnant or breast-feeding women will not be entered on this study.

          -  Any active uncontrolled infection

          -  Patients who are known to be serologically positive for Hepatitis A, B or C, or have a
             history of liver disease, other forms of hepatitis or cirrhosis.

          -  Known positive test for human immunodeficiency virus infection

          -  Patients with disease of any major organ system that would compromise their ability to
             withstand therapy

          -  Concurrent or prior (within 7 days of enrolment) anticoagulation therapy, except low
             molecular weight heparins or low dose aspirin

          -  Patients receiving corticosteroids must be on a stable dose that has not been
             increased for at least 7 days prior to study enrolment.

          -  Patients who are currently receiving another investigational drug are ineligible.

          -  Patients who are currently receiving other antineoplastic agents are ineligible.

          -  All herbal supplements, vitamins, and nutritional supplements taken within the last 30
             days prior to dosing on Day 1 (and continued use, if appropriate), must be reviewed
             and approved by the Study Chair.

          -  Patient will not be available for protocol-required study visits or procedures, to the
             best of the subject/parent/guardian's and investigator's knowledge.

          -  Patient has any kind of disorder that, in the opinion of the investigator, may
             compromise the ability of the subject/parent/guardian to give written informed consent
             and/or to comply with all required study procedures.

          -  History or evidence of any other clinically significant disorder, condition or disease
             (with the exception of those outlined above) that, in the opinion of the investigator
             would pose a risk to subject safety or interfere with the study evaluation, procedures
             or completion.

          -  Patients will be screened for antibodies to S. typhimurium and will not be eligible
             until antibodies are non-detectable

          -  Patients will be screened for IL6 and TNFa cytokines and will not be eligible until
             levels are less than 3x times the detectable limit of the assay.
      
Maximum Eligible Age:21 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0
Time Frame:Day 28 (cycle 1)
Safety Issue:
Description:To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR

Secondary Outcome Measures

Measure:Assess disease response according to RECIST version 1.1 for children with recurrent/refractory solid or CNS tumours
Time Frame:Up to 35 days after the completion of study treatment
Safety Issue:
Description:To preliminarily define the anti-tumour activity of EEDVSMit and assess response rates using RECIST version 1.1 criteria in children with recurrent/refractory solid or CNS tumours within the confines of a phase 1 study.
Measure:Assess overall survival
Time Frame:12 months from the date the last subject was enrolled in the study.
Safety Issue:
Description:Assess overall survival (OS) in children with recurrent/refractory solid or CNS tumours treated with EEDVSMit on this schedule
Measure:Time to response assessed by radiological imaging and RECIST v1.1
Time Frame:Evaluated at Day 56 (after cycle 2), then every second cycle to the end of study treatment (up to 12 months)
Safety Issue:
Description:Estimate the time to response.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dr David Ziegler

Trial Keywords

  • Recurrent
  • Refractory

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