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
|Condition or disease||Intervention/treatment||Phase|
|Solid Tumours CNS Tumours||Drug: Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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
- 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
- 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.
- 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.
- 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
- 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.
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 firstname.lastname@example.org|
|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|
|Study Chair:||David Ziegler, MBBS||Sydney Children's Hospitals Network|