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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]

ENG2

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Recurrent Glioblastoma Multiforme

Condition category

Condition code

Cancer

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]

Treatment: Drugs

Comparator / control treatment

None

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Assess six month progression free survival (6PFS) according to the Response Assessment in Neuro-Oncology (RANO) in recurrent GBM.

Timepoint [1]

6 months

Secondary outcome [1]

Assess response to therapy according to the RANO criteria

Timepoint [1]

At the end of each 8 week cycle

Secondary outcome [2]

Assess overall survival (OS) in patients with recurrent GBM

Timepoint [2]

Patients will be followed up every 3 months for 12 months after the last patients last visit.

Secondary outcome [3]

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]

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]

Determine the maximum tolerated dose (MTD) if feasible, of VEDVsDox in subjects with recurrent GBM

Timepoint [4]

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]

Estimate the time to response and duration of response as assessed by physical examination including neurological assessment and MRI scan.

Timepoint [5]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

EnGeneIC Ltd

Address [1]

Building 2, 25 Sirius Road
Lane Cove
NSW 2066

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

MELBOURNE HEALTH HUMAN RESEARCH ETHICS COMMITTEE

Ethics committee address [1]

PO Royal Melbourne Hospital
Parkville Victoria 3050

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/08/2012

Approval date [1]

03/10/2012

Ethics approval number [1]

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

Prof Mark Rosenthal

Address

Director of Medical Oncology
Royal Melbourne Hospital
Grattan Street
Parkville
Victoria
Australia 3050

Country

Australia

Phone

+61-3-9342 7695

Fax

[email protected]

Contact person for public queries

Name

Helen Foster

Address

Clinical Trial Coordinator,
EnGeneIC Pty Limited, Cancer Therapeutics
Building 2, 25
Sirius Road
Lane Cove West.
NSW. 2066.

Country

Australia

Phone

+612 8203 5033

Fax

[email protected]

Contact person for scientific queries

Name

Jennifer MacDiarmid

Address

EnGeneIC Ltd
Cancer Therapeutics
Building 2, 25 Sirius Road
Lane Cove West.
NSW. 2066. Australia

Country

Australia

Phone

+612 9420 5844

Fax

[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

Source	Title	Year of Publication	DOI
Dimensions AI	Ligand-targeted particulate nanomedicines undergoing clinical evaluation: Current status	2013	https://doi.org/10.1016/j.addr.2013.08.012

N.B. These documents automatically identified may not have been verified by the study sponsor.

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