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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02687386




Registration number
NCT02687386
Ethics application status
Date submitted
28/01/2016
Date registered
22/02/2016
Date last updated
24/06/2019

Titles & IDs
Public title
A Study of Intravenous EEDVsMit in Children With Recurrent / Refractory Solid or CNS Tumours Expressing EGFR
Scientific 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)
Secondary ID [1] 0 0
KCA001
Universal Trial Number (UTN)
Trial acronym
ECREST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Solid Tumours 0 0
CNS Tumours 0 0
Condition category
Condition code
Cancer 0 0 0 0
Brain
Cancer 0 0 0 0
Children's - Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mitoxantrone packaged EDV (EnGeneIC Delivery Vehicle)

Experimental: Mitoxantrone packaged EDV - Mitoxantrone packaged EDV (EnGeneIC Dream Vector)


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
MTD at which fewer than one third of patients experience dose limiting toxicity as assessed by CTCAE v4.0 - To determine a recommended phase 2 dose (RP2D) for EEDVsMit administered intravenously in children with recurrent / refractory solid or CNS tumours expressing EGFR
Timepoint [1] 0 0
Day 28 (cycle 1)
Primary outcome [2] 0 0
Incidence of treatment-related adverse events as assessed by CTCAE v4.0 - To define and describe the toxicities of EEDVSMit administered on these schedules in children with recurrent/refractory solid or CNS tumours
Timepoint [2] 0 0
Up to 35 days after the completion of study treatment
Primary outcome [3] 0 0
Incidence of all adverse events as assessed by CTCAE v4.0, clinically significant changes in vital signs, ECGs and clinical laboratory tests - Assess the safety and tolerability of EEDVSMit in children with recurrent/refractory solid or CNS tumours.
Timepoint [3] 0 0
Up to 35 days after the completion of study treatment
Secondary outcome [1] 0 0
Assess disease response according to RECIST version 1.1 for children with recurrent/refractory solid or CNS tumours - 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.
Timepoint [1] 0 0
Up to 35 days after the completion of study treatment
Secondary outcome [2] 0 0
Assess overall survival - Assess overall survival (OS) in children with recurrent/refractory solid or CNS tumours treated with EEDVSMit on this schedule
Timepoint [2] 0 0
12 months from the date the last subject was enrolled in the study.
Secondary outcome [3] 0 0
Time to response assessed by radiological imaging and RECIST v1.1 - Estimate the time to response.
Timepoint [3] 0 0
Evaluated at Day 56 (after cycle 2), then every second cycle to the end of study treatment (up to 12 months)

Eligibility
Key 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
Minimum age
2 Years
Maximum age
21 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Sydney Children's Hospital - Randwick
Recruitment hospital [2] 0 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
- Westmead

Funding & Sponsors
Primary sponsor type
Other
Name
Dr David Ziegler
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Engeneic Pty Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02687386
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Ziegler, MBBS
Address 0 0
Sydney Children's Hospitals Network
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Ziegler, MBBS
Address 0 0
Country 0 0
Phone 0 0
+61 2 9382 1730
Fax 0 0
Email 0 0
d.ziegler@unsw.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02687386