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Trial registered on ANZCTR


Registration number
ACTRN12613001249741
Ethics application status
Approved
Date submitted
12/11/2013
Date registered
13/11/2013
Date last updated
2/09/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A feasibility and efficacy study of anti-human Epidermal Growth Factor Receptor (Vectibix sequence) targeted EnGeneIC Delivery Vehicle (also known as EnGeneIC Dream Vector) containing clinician chosen therapeutic payload(s) (cytotoxic drug or functional nucleic acids) in patients with advanced cancer who have no curative treatment options.
Scientific title
A Phase 1 study of anti-human EGFR (Vectibix sequence) targeted EDVs carrying cytotoxic drug, siRNA or miRNA (VEDVsPayload) in Patients with Advanced Solid Tumours who have no curative treatment options.
Secondary ID [1] 283526 0
ENG4
Universal Trial Number (UTN)
Trial acronym
Tailored EDV
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid tumours 290438 0
Condition category
Condition code
Cancer 290827 290827 0 0
Other cancer types

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The EnGeneIC Delivery Vehicle™, also known as EnGeneIC Dream Vector™ (EDV™) is a bacterially-derived nanoparticle drug, siRNA or miRNA delivery system, designed to directly target and effectively kill tumour cells with minimal toxicity, while at the same time stimulate the immune system's natural anti-tumour response.
Intravenously injected EDV nanocells exit the leaky vascular system found within tumours and attach to cancer cells via a specially designed, targeted bi-specific antibody. Once attached, the nanocell is able to enter the tumour cell and deliver the payload of chemotherapy, siRNA, or miRNA or a combination of these. In parallel, the bacterial cell wall of the nanocells stimulates key components of the immune system, which are then activated to seek out and destroy cancer cells.
The Tailored EDV study (ENG4) is an open-label feasibility study of a single delivery agent vEDVsPayload containing clinician chosen therapeutic payload(s) (cytotoxic drug, siRNA or miRNA) in eligible patients with advanced solid tumours, who have no curative treatment options.
Eligibility requires patients to have an archived, or incidentally collected at elective surgery, tumour sample(s) (paraffin block or slide) for analysis of Epidermal Growth Factor Receptor (EGFR) expression. In addition, radiological assessment by MRI, CT or PET scan confirming measurable disease is also required for study entry.
There are four potential cytotoxics, in addition to potent anti-tumour siRNA or miRNA, that can be individually selected as the payload; Maytansinoid, Doxorubicin, Mitoxantrone and Gemcitabine. The VEDV can be packaged with a single or multiple payload, dependent on the pre-identified sensitivity of a patients cancer cells to one or more of the cytotoxic agents, uniquely targeting the individual’s disease.
All patients will commence on a starting dose of 2x10^9 VEDVsPayload. If the patient tolerates this initial dose level, subsequent doses can be increased to 5x10^9 VEDVsPayload.at the discretion of the Investigator.
VEDVsPayload will be administered once per week for 8 weeks, via an intravenous 20 minute infusion, which will equate to 1 treatment cycle. Tumour evaluation is to be performed at week 9 using the same method of assessment as at screening; CT, PET or MRI scan.
If the patient does not fulfill any of the criteria for withdrawal they may continue to receive further cycles of VEDVsPayload. Cycle 2 will recommence at Week 10 with IV VEDVsPayload to be administered weekly for 8 weeks, unless the patient becomes intolerant to the study medication or the patient withdraws consent, for up to a maximum treatment period of 12 months. Tumour evaluations by MRI, CT or PET scan will be performed every 9 weeks.
The primary completion of the study for the primary analysis will occur after all patients have either completed the study or 6 months of treatment. A safety follow-up visit must be performed 30 - 35 days after the last dose of VEDVsPayload.
All patients that discontinue Investigational product and have not withdrawn consent to participate in the study, will continue in the long term follow-up phase. Long term follow-up will occur every 3 months from 30-35 day follow up visit for 12 months and then for the extent of patient survival.
Intervention code [1] 288222 0
Treatment: Drugs
Comparator / control treatment
None
Control group
Uncontrolled

Outcomes
Primary outcome [1] 290838 0
Assess anti-tumour response and overall survival (OS) in patients with advanced solid tumours who have run out of all treatment options.

This is a composite primary outcome.

The primary outcome will be assessed by baseline imaging using MRI, CT or PET scans of the known tumour sites of disease as well as scans of the chest, abdomen and pelvis if not already performed. MRI or PET scans may be used for tumour assessment if felt to delineate disease better. Scans will be repeated after each 8 week cycle (Week 9). The same method of assessment and the same technique will be used to characterise each identified lesion at baseline and subsequent assessments. Disease responses will be categorised using RECIST criteria (Version 1.1)..
Timepoint [1] 290838 0
Anti-tumour response will be assessed after each 8 week cycle (Week 9) during treatment phase.
Secondary outcome [1] 305400 0
Assess the safety and tolerability of VEDVs carrying different therapeutic payloads in patients with advanced solid tumours.
Timepoint [1] 305400 0
All subjects will be closely monitored for adverse events and under go safety assessments whilst on study treatment, in accordance with the protocol schedule.
Safety data will be reviewed after each 5 subjects have enrolled. Each review will include all available data on the incidence of adverse events (including serious, treatment-related, and events requiring the discontinuation of investigational product). All subjects will be asked to complete a safety follow-up visit 30-35 days after withdrawal from study treatment.

Eligibility
Key inclusion criteria
Adult patients with histologically or cytologically confirmed advanced solid tumour that are metastatic or unresectable and for which standard curative or palliative measures are not available or are no longer effective. Participants will have an archived, or recent primary or metastatic tumour biopsy sample(s) (paraffin block or slide) for analysis of Epidermal Growth Factor Receptor (EGFR) expression. Postivie EGFR expression is not a pre-requisite for study inclusion. In addition, radiological assessment by MRI, CT or PET scan confirming measurable disease is also required for study entry.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Prior therapy with an EGFR inhibitor within 30 days prior to first dose;
2. Patients who have received treatment with anti-angiogenic agents within 6 weeks prior to the first dose;
3. Patients who have received treatment with Immunotherapeutic agents or monoclonal antibody therapy within 4 weeks before enrollment or have not recovered from the toxic effects of such cancer therapy;
4. Patients who have received treatment with alkylating agents within 6 weeks before enrollment or has not recovered from the toxic effects of such cancer therapy;
5. Patients who have received chemotherapy or radiotherapy, within 4 weeks of study entry;
6. Previous exposure to the payload of the particular Investigational agent.
7.. Patients who have had vaccination against Salmonella serovars within 12 months of study entry or patients who are positive for antibodies to salmonella species;
8. Patients with significant pericardial effusions, pleural effusions or ascites.
9. Unstable diabetes mellitus or other contraindications for the use of dexamethasone.
10. Uncontrolled concurrent cardiac disease including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.

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
Phase
Phase 1
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The Sponsor has decided to close the study early, due to request from HREC to submit a new protocol rather than a substantial protocol amendment to ENG4. The Sponsor will submit a new protocol which will incorporate the addition of a new adjuvant therapy that it is hypothesised will augment the anti-tumour effect of EDV based therapy.
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] 5303 0
Northern Cancer Institute - St Leonards
Recruitment postcode(s) [1] 12213 0
2065 - St Leonards

Funding & Sponsors
Funding source category [1] 288224 0
Commercial sector/Industry
Name [1] 288224 0
EnGeneIC Pty. Limited
Address [1] 288224 0
Building 2, 25 Sirius Road Lane Cove NSW 2066
Country [1] 288224 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Pty Limited
Address
Building 2, 25 Sirius Road Lane Cove NSW 2066
Country
Australia
Secondary sponsor category [1] 286947 0
None
Name [1] 286947 0
Address [1] 286947 0
Country [1] 286947 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290133 0
Bellberry Human Research Ethics Committee
Ethics committee address [1] 290133 0
129 Glen Osmond Road Eastwood South Australia 5063
Ethics committee country [1] 290133 0
Australia
Date submitted for ethics approval [1] 290133 0
05/11/2013
Approval date [1] 290133 0
14/11/2014
Ethics approval number [1] 290133 0

Summary
Brief summary
The Tailored EDV study (ENG4) is an open-label feasibility study of a single delivery agent VEDVsPayload containing clinician chosen therapeutic payload(s) (cytotoxic drug, siRNA or miRNA).

Who may be eligible? Participants must have histological or cytological confirmed advanced solid tumours, who have no curative treatment options. Eligibility also requires participants to have an archived tumour sample(s), or recent primary or metastatic tumour biopsies, (paraffin block or slide) for analysis of Epidermal Growth Factor Receptor (EGFR) expression. In addition, radiological assessment by MRI, CT or PET scan confirming measurable disease is required for study entry.

Study details: Participants will receive VEDVsPayload once a week for 8 weeks, via a 20 minute intravenous infusion. This is known as 1 treatment cycle. There are four potential cytotoxic chemotherapy drugs, in addition to potent anti-tumour siRNA or miRNA, that can be individually selected as the VEDV payload. The VEDV can be packaged with a single or multiple payload, dependent on the pre-identified sensitivity of a patients cancer cells to one or more of the cytotoxic agents, so uniquely targeting the individual’s disease.
The investigational treatment is given as an out-patient. Participants will be monitored closely for any adverse effects by the collection of regular blood tests to monitor haematological and liver function, in addition to physical examinations and monitoring of vital signs (including resting pulse, respirations, blood pressure and temperature). Participants will be required to spend between 4 and 6 hours in the hospital at each visit.
Tumour evaluation using the same method of assessment as at screening, MRI, CT or PET scan, will be performed every 9 weeks (after each 8 week treatment cycle).
If the patient does not fulfill any of the criteria for withdrawal they may continue to receive further cycles of VEDVsPayload for up to a maximum treatment period of 12 months.
If new in-vitro data emerges from the testing of patient’s tumour samples collected either from biopsy or from circulating tumour cells, then this data will be regularly reviewed by clinical treating team and the chief scientists at EnGeneIC Pty Limited. If the data suggests that the patient may derive increased clinical benefit by combining or changing the therapeutic payload packaged in VEDVs, then the patient may receive treatment with a different VEDVsPayload.

Follow-up: A safety follow-up visit will be performed 30 - 35 days after the last dose of VEDVsPayload. All patients that discontinue Investigational product and have not withdrawn consent to participate in the study, will continue in the long term follow-up phase every 3 months.
Trial website
http://www.engeneic.com/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44094 0
Prof Stephen Clarke
Address 44094 0
Northern Cancer Institute, Level 1 38 Pacific Highway, St. Leonards, NSW 2065, Australia
Country 44094 0
Australia
Phone 44094 0
+61 2 9463 1172
Fax 44094 0
Email 44094 0
stephen.clarke@sydney.edu.au
Contact person for public queries
Name 44095 0
Ms Helen Foster
Address 44095 0
Clinical Trial Coordinator,
EnGeneIC Pty. Limited,
Building 2, 25
Sirius Road,
Lane Cove West,
NSW 2066
Country 44095 0
Australia
Phone 44095 0
+612 8203 5033
Fax 44095 0
Email 44095 0
hfoster@engeneic.com
Contact person for scientific queries
Name 44096 0
Dr Jennifer MacDiarmid
Address 44096 0
EnGeneIC Ltd Cancer Therapeutics Building 2, 25 Sirius Road Lane Cove West. NSW. 2066. Australia
Country 44096 0
Australia
Phone 44096 0
+612 9420 5844
Fax 44096 0
Email 44096 0
jmacdiarmid@engeneic.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary