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)
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)
EnGeneIC Ltd
46 participants
Feb 8, 2013
Interventional
Conditions
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.
Eligibility
Inclusion Criteria1
- Patients with pathologically documented, and definitively diagnosed recurrent WHO Grade IV advanced malignant GBM which expresses EGFR.
Exclusion Criteria1
- 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
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Interventions
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.
Locations(1)
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ACTRN12613000297729