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

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ClinicalTrials.gov Identifier: NCT02687386
Recruitment Status : Recruiting
First Posted : February 22, 2016
Last Update Posted : October 24, 2017
Information provided by (Responsible Party):

Study Description
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Solid Tumours CNS Tumours Drug: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle) Phase 1

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).

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)
Study Start Date : February 2016
Estimated Primary Completion Date : February 2021
Estimated Study Completion Date : April 2021

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Experimental: Mitoxantrone packaged EDV
Mitoxantrone packaged EDV (EnGeneIC Dream Vector)
Drug: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)
EnGeneIC Delivery Vehicles (EDVs) are nanocells which can be loaded with anti-cancer drugs (mitoxantrone in this study) and targeted to tumor cells. These bacterially-derived nanocells are coated in bispecific antibodies (BsAb) that recognize oncogenic receptors on the tumor cell surface. Once bound to the tumour cell, the targeted and drug-loaded EDVs are endocytosed and release their toxic payload to destroy the tumor cell.
Other Name: EDV also stands for EnGeneIC Dream Vector

Outcome Measures

Primary Outcome Measures :
  1. 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) ]
    To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR

  2. Incidence of treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 35 days after the completion of study treatment ]
    To define and describe the toxicities of EEDVSMit administered on these schedules in children with recurrent/refractory solid or CNS tumours

  3. Incidence of all adverse events as assessed by CTCAE v4.0, clinically significant changes in vital signs, ECGs and clinical laboratory tests [ Time Frame: Up to 35 days after the completion of study treatment ]
    Assess the safety and tolerability of EEDVSMit in children with recurrent/refractory solid or CNS tumours.

Secondary Outcome Measures :
  1. 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 ]
    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.

  2. Assess overall survival [ Time Frame: 12 months from the date the last subject was enrolled in the study. ]
    Assess overall survival (OS) in children with recurrent/refractory solid or CNS tumours treated with EEDVSMit on this schedule

  3. 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) ]
    Estimate the time to response.

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT02687386

Contact: David Ziegler, MBBS +61 2 9382 1730 d.ziegler@unsw.edu.au
Contact: Dominique Hess, PhD +61 2 9382 3122 Dominique.Hess@health.nsw.gov.au

Australia, New South Wales
Sydney Children's Hospital Recruiting
Randwick, New South Wales, Australia, 2031
Contact: David Ziegler, MBBS    +61293821730      
Contact: Dominique Hess, PhD    +61293823122    Dominique.Hess@health.nsw.gov.au   
Principal Investigator: David Ziegler, MBBS         
Sub-Investigator: Toby Trahair, MBBS         
The Children's Hospital at Westmead Recruiting
Westmead, New South Wales, Australia
Principal Investigator: Geoff McCowage         
Sponsors and Collaborators
Dr David Ziegler
Engeneic Pty Limited
Study Chair: David Ziegler, MBBS Sydney Children's Hospitals Network
More Information

Responsible Party: Dr David Ziegler, Chief Investigator, Sydney Children's Hospitals Network
ClinicalTrials.gov Identifier: NCT02687386     History of Changes
Other Study ID Numbers: KCA001
First Posted: February 22, 2016    Key Record Dates
Last Update Posted: October 24, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: De-identified data is planned to be shared with EnGeneIC.

Keywords provided by Dr David Ziegler, Sydney Children's Hospitals Network:

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action