None listed
Conditions
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.
Interventions
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 a
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.
Sponsors
EnGeneIC Pty Limited
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Outcome results
None listed