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Trial registered on ANZCTR


Registration number
ACTRN12613000297729
Ethics application status
Approved
Date submitted
6/03/2013
Date registered
18/03/2013
Date last updated
12/11/2015
Type of registration
Retrospectively registered

Titles & IDs
Public title
A Phase 1/2 study to determine the effect of Doxorubicin loaded EnGeneIC Delivery Vehicles on progression free survival in Patients with Recurrent Glioblastoma Multiforme (GBM)
Scientific title
A Phase 1/2 study to determine the effect of EGFR targeted Doxorubicin loaded EnGeneIC Delivery Vehicles (VEDVDox) on progression free survival in Patients with Recurrent Glioblastoma Multiforme (GBM) Expressing Epidermal Growth Factor Receptor (EGFR)
Secondary ID [1] 282081 0
ENG2
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Recurrent Glioblastoma Multiforme 288575 0
Condition category
Condition code
Cancer 288909 288909 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Anti-human EGFR (vectibix sequence)EDV'sDox (VEDVsDox) An EDV is an anucleate bacterially derived minicell. EDVs can be loaded with chemotherapy, in this case Doxorubicin. The EDV is coated with EGFR antibodies to enable it to attach to cancer cells. Eligible subjects enrolled in the study will receive VEDVsDox IV weekly as a 20 min infusion beginning at study day 1. Following the first eight doses (1 cycle) of VEDVsDox, subjects will undergo radiological assessment of their tumors with MRI prior to commencing Cycle 2. Dosing with VEDVsDox may resume at week 9 and continue until there is radiographic evidence of progressive disease (PD) per RANO criteria, 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 withdraws consent. Subsequent tumor evaluations by MRI will occur at every 8 weeks thereafter.

The study will be conducted in two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Part 1 – Dose Exploration
The dose exploration part of the study is aimed at determining the maximum tolerated dose (MTD) in this patient group. A standard dose escalation with a 3x3 design will be used.

Part 1 will commence dosing at 2x10^9 VEDVsDox and escalate to 5x10^9 VEDVsDox evaluating the safety and tolerability, of VEDVsDox. Consideration will be given to further dose escalations and the possibility of exploring intermediate or lower doses depending on the safety profile.

Part 2 Dose expansion:
The dose expansion phase (Part 2) will begin upon completion of the dose exploration (Part 1). Up to 46 subjects with recurrent GBM will be treated at the Recommended Phase Two Dose (RPTD) (combining subjects enrolled in Parts 1 and 2). The sample size in the dose expansion part will vary depending on the number of subjects in Part 1 treated.
Intervention code [1] 286681 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289036 0
Assess six month progression free survival (6PFS) according to the Response Assessment in Neuro-Oncology (RANO) in recurrent GBM.
Timepoint [1] 289036 0
6 months
Secondary outcome [1] 301613 0
Assess response to therapy according to the RANO criteria
Timepoint [1] 301613 0
At the end of each 8 week cycle
Secondary outcome [2] 301614 0
Assess overall survival (OS) in patients with recurrent GBM
Timepoint [2] 301614 0
Patients will be followed up every 3 months for 12 months after the last patients last visit.
Secondary outcome [3] 301615 0
Assess the safety and tolerability of VEDVsDox in patients with recurrent GBM. Examples of possible adverse events that may be related to treatment include transaminitis, transient hypophosphataemia and fevers.
Timepoint [3] 301615 0
Spontaneously reported adverse events may be reported at any time after the first administration of study treatment. Adverse events will also be elicited at 3 hours after each dose administration and up to 30 days after the last dose.
Secondary outcome [4] 301616 0
Determine the maximum tolerated dose (MTD) if feasible, of VEDVsDox in subjects with recurrent GBM
Timepoint [4] 301616 0
Patients in part 1 of the study (dose exploration phase) will have their safety information reviewed after the first 28 days on study
Secondary outcome [5] 301617 0
Estimate the time to response and duration of response as assessed by physical examination including neurological assessment and MRI scan.
Timepoint [5] 301617 0
At the end of each 8 week cycle

Eligibility
Key inclusion criteria
Patients with pathologically documented, and definitively diagnosed recurrent WHO Grade IV advanced malignant GBM which expresses EGFR.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous treatment with bevacizumab or anti-angiogenic therapy, treatment with immunotherapeutic agents, vaccines, or monoclonal antibody in past 4 weeks. Known allergy or sensitivity to any of the excipients in the investigational product

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
Other design features
Part 1 dose exploration
Part 2 dose expansion
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Date of first participant enrolment
Anticipated
5/02/2013
Actual
8/02/2013
Date of last participant enrolment
Anticipated
Actual
26/08/2013
Date of last data collection
Anticipated
Actual
Sample size
Target
46
Accrual to date
Final
14
Recruitment in Australia
Recruitment state(s)
NSW,VIC

Funding & Sponsors
Funding source category [1] 286858 0
Commercial sector/Industry
Name [1] 286858 0
EnGeneIC Ltd
Country [1] 286858 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Ltd
Address
Building 2, 25 Sirius Road
Lane Cove
NSW 2066
Country
Australia
Secondary sponsor category [1] 285647 0
None
Name [1] 285647 0
Address [1] 285647 0
Country [1] 285647 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288920 0
MELBOURNE HEALTH HUMAN RESEARCH ETHICS COMMITTEE
Ethics committee address [1] 288920 0
PO Royal Melbourne Hospital
Parkville Victoria 3050
Ethics committee country [1] 288920 0
Australia
Date submitted for ethics approval [1] 288920 0
29/08/2012
Approval date [1] 288920 0
03/10/2012
Ethics approval number [1] 288920 0
HREC/12/MH/252

Summary
Brief summary
This study looks at treatment with a targeted biological therapy (Anti-Human Epidermal Growth Factor Receptor (Vectibix sequence) Targeted, Doxorubicin Loaded EnGeneIC Delivery Vehicles [VEDVsDox]) in people with recurrent Glioblastoma Multiforme (GBM).

Who is it for?
Patients may be able to join this study if they have recurrent WHO Grade IV advanced malignant GBM which expresses EGFR.

Trial details
The study will be conducted in two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion. Part 1 of the study is aimed at determining the maximum tolerated dose (MTD). It will commence dosing at 2x10^9 VEDVsDox and escalate to 5x10^9 VEDVsDox evaluating the safety and tolerability of VEDVsDox. The dose expansion phase (Part 2) will begin upon completion of the dose exploration (Part 1) and up to 46 subjects with recurrent GBM will be treated at the Recommended Phase Two Dose (RPTD)

The treatment phase of both parts of the trial is divided into cycles. Each cycle is 8 weeks long and will require that the patient come to the hospital to receive the study treatment every week for 8 weeks. This will involve an intravenous injection (injection into a vein) of a 20mL of EDVs over a period of 20 minutes.
The time spent at each hospital visit will vary and may be between 1 and 5 hours. During the treatment phase at various times the patient will have the following procedures performed:
* An MRI scan every 8 weeks;
* A physical examination, weight and a neurological examination;
* Blood sample collection of 40ml (2 tablespoons) and urine sample collection and testing to assess overall health;
*Electrocardiogram (ECG) to assess the health of the patients heart;
*Vital signs including resting pulse, respiration, blood pressure, temperature will be measured;
* Patients will be asked questions about quality of life and any side effects;
* Blood sample collection of 9ml (1/2 tablespoon) for pharmacokinetic analysis in the first cycle only.

The Patient may continue to receive cycles of study treatment for as long as the cancer remains stable or continues to reduce in size, and they are tolerating the treatment.
When the patient has stopped treatment they will be asked to return to the hospital for a safety follow-up visit approximately 1 month after the last study treatment. This visit will be similar to the treatment visits.
Trial website
Trial related presentations / publications
Whittle JR et al. First in human nanotechnology doxorubicin delivery system to target epidermal growth factor receptors in recurrent glioblastoma. J Clin Neurosci (2015)
Public notes

Contacts
Principal investigator
Name 38342 0
Prof Mark Rosenthal
Address 38342 0
Director of Medical Oncology
Royal Melbourne Hospital
Grattan Street
Parkville
Victoria
Australia 3050
Country 38342 0
Australia
Phone 38342 0
+61-3-9342 7695
Fax 38342 0
Email 38342 0
[email protected]
Contact person for public queries
Name 38343 0
Helen Foster
Address 38343 0
Clinical Trial Coordinator,
EnGeneIC Pty Limited, Cancer Therapeutics
Building 2, 25
Sirius Road
Lane Cove West.
NSW. 2066.
Country 38343 0
Australia
Phone 38343 0
+612 8203 5033
Fax 38343 0
Email 38343 0
[email protected]
Contact person for scientific queries
Name 38344 0
Jennifer MacDiarmid
Address 38344 0
EnGeneIC Ltd
Cancer Therapeutics
Building 2, 25 Sirius Road
Lane Cove West.
NSW. 2066. Australia
Country 38344 0
Australia
Phone 38344 0
+612 9420 5844
Fax 38344 0
Email 38344 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
Dimensions AILigand-targeted particulate nanomedicines undergoing clinical evaluation: Current status2013https://doi.org/10.1016/j.addr.2013.08.012
N.B. These documents automatically identified may not have been verified by the study sponsor.