Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000779471
Ethics application status
Approved
Date submitted
23/06/2025
Date registered
24/07/2025
Date last updated
24/07/2025
Date data sharing statement initially provided
24/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
A study in participants with glioblastoma that has progressed after standard of care therapy, looking at the safety and effect of treatment with the experimental drug E-EDV-Dox/GC or EnGeneIC Dream Vectors (EDVs) packaged with the chemotherapy (Doxorubicin) given simultaneously with non-targeted EDVs carrying an immune enhancer called EDV-GC. (EDV-GBM Trial)
Scientific title
A Phase I/IIa Study of EGFR-targeted EDVs Carrying Doxorubicin (E-EDV-Dox) Combined with EDVs Carrying a-Galactosyl Ceramide (EDV-GC) in People with Recurrent Glioblastoma.
Secondary ID [1] 314715 0
EDV-GBM Trial
Universal Trial Number (UTN)
Trial acronym
ENG20
Linked study record
This record is a follow-up study of ACTRN12613000297729 with the addition of EDVs loaded with the adjuvant a-galactosyl ceramide (EDV-GC).

Health condition
Health condition(s) or problem(s) studied:
Recurrent Glioblastoma 337911 0
Condition category
Condition code
Cancer 334240 334240 0 0
Brain

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is testing an experimental treatment for people with a type of brain cancer called glioblastoma that has returned or progressed after the failure of standard of care therapy. The experimental treatment consists of a chemotherapy drug, Doxorubicin, packaged inside an EGFR targeted delivery vehicle to form the investigational product E-EDV-Dox. The EDV delivery vehicle is used to transport the chemotherapy directly to the brain tumor where it attaches to the surface of EGFR expressing cancer cells causing the cancer cell to die.

The E-EDV-Dox are given at the same time as one other investigational product designed to boost the body's own immune system to fight the cancer. This investigational product consists of non-targeted EDVs carrying a-galactosyl ceramide or EDV-GC.
The combination of these 2 drugs is known as E-EDV-Dox/GC.
The study aims to evaluate the safety and efficacy of E-EDV-Dox/GC in patients with confirmed grade IV glioblastoma or high-grade glioma with features consistent with glioblastoma at time of first diagnosis. The study is designed with two phases, Phase I (dose assessment) and Phase IIa (dose expansion). In Phase I of the study a safety assessment will be performed on 6 participants, while in Phase II the recommended dosing regimen from Phase I will be open to a maximum of 40 participants. Participants in the phase IIa dose expansion part of the trial will follow the same treatment cycle visit schedule regardless of the recommended dose level.

The first treatment cycle will involve bi-weekly visits for 4 weeks, followed by weekly visits for 3 weeks. Doses of E-EDV-Dox/GC in 3mL of 0.9% sodium chloride are administered intravenously over 10 seconds. The first dose of E-EDV-Dox/GC at Cycle 1 will be given at a reduced dose of 1.5 x10^9 and subsequent doses will be escalated incrementally as 2.5 x10^9, 3.75 x10^9, 4.75 x10^9, 6.0 x10^9, 7.0 x10^9 until the target dose level of 8.0 x10^9 E-EDV-Dox/GC is attained at Dose 7, Week 4. Intra-cycle dose escalation will be used for all participants in Cycle 1 only. For weeks 5-7, visits will occur once/week where 2 doses of 8.0 x10^9 E-EDV-Dox/GC will be administered 90 minutes apart during each visit.

In week 8, tumour burden will be radiologically re-evaluated in accordance with Response Assessment in Neuro-Oncology (RANO 2.0) guidelines to determine treatment response.

Subsequent treatment cycles will consist of weekly visits for 7 weeks where two doses will be administered at each visit 90 minutes apart. Following each 7-week treatment period is a treatment free week in which tumour burden is radiologically re-assessed (Week 8). Treatment may continue until the patient or investigator deems it suitable to stop treatment, for example if serious side effects occur or if the participants disease continues to grow.

It is estimated that the study duration for participants in the active treatment phase will be approximately 6 months consisting of two weeks for screening, 16 weeks of treatment (2 cycles), depending on the disease state and tolerability to the IMP and a 30-35-day safety follow-up visit.

The study will monitored to evaluate the study conduct and ensure adherence to the protocol and compliance with ICH GCP guidelines. Case Report Forms, medical records and study related material will be reviewed at regular intervals throughout the study to verify adherence to the protocol; completeness, accuracy, and consistency of the data.

Any adverse events will be monitored, and ongoing safety evaluations will be conducted by a designated Safety Monitoring Board, who will assess the progress of the trial and will be responsible for decisions as whether to continue, modify, or stop the trial.
This study is designed as a Phase I/IIa trial, with a 6-patient safety run in for Phase I. If greater than or equal to two of the first six evaluable patients experience a DLT the Safety Monitoring Board will review the accumulated safety data to determine whether the maximum dose applied during the study will be reduced. The committee will consist of the Principal Investigator and/or Co-Investigator(s), one independent oncologist with experience in Phase I/IIa studies, and at least one Sponsor representative. Each review will include all available data on the incidence of AEs (including SARs, DLTs, lab and vital sign data and events requiring the discontinuation of IMP) and deaths.

If the Safety Monitoring Board are satisfied that the requirements for dose safety and tolerability have been met in recurrent glioblastoma, then the study will continue to enroll up to 46 participants. Participants in the Phase IIa dose expansion part of the trial will follow the same treatment cycle visit schedule regardless of the recommended dose level.
Intervention code [1] 331323 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 341905 0
To assess the incidence and severity of Adverse Events
Timepoint [1] 341905 0
All adverse Events will be assessed for each participant at every study visit from the day of first dose (Day 1) until the safety follow up visit 30-35 days after the final dose.
Secondary outcome [1] 448930 0
Overall Survival (OS)
Timepoint [1] 448930 0
Any deaths occurring after the commencement of study drug will be recorded appropriately, and survival will continue to be monitored every 3 months from the safety follow-up visit, for a period of 12 months, and then for the extent of subject survival.
Secondary outcome [2] 448931 0
To assess the six month progression free survival
Timepoint [2] 448931 0
Radiological imaging taken at baseline, 8 weeks, 16 weeks and 24 weeks after the commencement of study drug.
Secondary outcome [3] 448937 0
To assess the disease control rate
Timepoint [3] 448937 0
Radiological imaging will occur at baseline, then every 8 weeks after the commencement of study drug and at the safety follow up visit, 30-35 days after the final dose of study drug.
Secondary outcome [4] 448944 0
Health related quality of life outcome will be assessed as a composite outcome
Timepoint [4] 448944 0
Quality of life will be measured at baseline, every 4 weeks after the commencement of study drug and at the safety follow-up visit, 30-35 days after the final dose of study drug.

Eligibility
Key inclusion criteria
-Histologically confirmed WHO grade IV glioblastoma or high grade glioma with molecular features consistent with glioblastoma.
-Confirmed recurrence or progression.
-Measurable disease per RANO 2.0 criteria.
-Karnofsky performance status (KPS) score of 70 or higher.
-Adequate haematological function.
-Adequate renal function.
-Adequate hepatic function.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
-Early disease progression prior to 3 months (12 weeks) from the completion of radiotherapy.
-History of central nervous system bleeding within 6 months prior to enrolment.
-Evidence of acute intracranial / intra-tumoral hemorrhage, except for participants with stable grade 1 hemorrhage.
-History of significant bleeding disorder.
-Participant has a history of coronary artery disease, with or without angina pectoris or myocardial infarction, symptomatic congestive heart failure (New York Heart Association > class II), uncontrolled hypertension (systolic > 140 mmHg or diastolic > 90 mmHg) or a history of hypertensive crises, or cardiac arrhythmias requiring anti-arrhythmic therapy.
-Clinically significant electrocardiogram (ECG) changes at enrolment which obscure the ability to assess the PR, QT, and QRS interval, congenital long QT syndrome.
-History of thromboembolic events, including arterial (e.g., stroke, myocardial infarction) or venous thromboembolism within last six months.
-Participant has an active infection requiring treatment.
-History of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer, or other malignancies curatively treated with no evidence of disease for greater than or equal to 2 years.
-History of gastrointestinal perforation, fistula formation or intra-abdominal abscess within 6 months prior to Study Day 1.
-Participant has received immunotherapeutic agents, vaccines, or monoclonal antibody therapy (within 4 weeks of Study Day 1 or has not recovered from the toxic effects of such cancer therapy), anticoagulation therapy (within 7 days of Study Day 1), except low molecular weight heparins or low dose aspirin, other investigational therapy (within 30 days of Study Day 1). Any major surgery (within 4 weeks of Study Day 1, or has not recovered from the effects of such surgery). Any minor surgery within 7 days of Study Day 1.
-The participant has a known allergic/hypersensitivity to investigational components or excipients e.g. doxorubicin, trehalose, or monoclonal antibody therapy.
-Females who are pregnant or breastfeeding.
-Subjects who cannot comply with protocol scheduled study visits or procedures, to the best of the subject and Investigator’s knowledge.

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
Single group
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/08/2025
Actual
Date of last participant enrolment
Anticipated
30/07/2027
Actual
Date of last data collection
Anticipated
4/02/2028
Actual
Sample size
Target
46
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 28135 0
Frankston Private Hospital - Frankston
Recruitment hospital [2] 28136 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 44341 0
3199 - Frankston
Recruitment postcode(s) [2] 44342 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 319271 0
Commercial sector/Industry
Name [1] 319271 0
EnGeneIC Pty Ltd
Country [1] 319271 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Pty Ltd
Address
Country
Australia
Secondary sponsor category [1] 321742 0
None
Name [1] 321742 0
Address [1] 321742 0
Country [1] 321742 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 317846 0
Bellberry Human Research Ethics Committee A
Ethics committee address [1] 317846 0
Ethics committee country [1] 317846 0
Australia
Date submitted for ethics approval [1] 317846 0
07/05/2025
Approval date [1] 317846 0
13/06/2025
Ethics approval number [1] 317846 0
2025-05-715

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142338 0
A/Prof Vinod Ganju
Address 142338 0
Peninsula And Southeast Oncology Suites (PASO), Frankston Private Hospital, Suite 7, Level 3, 5 Susono Way Frankston, VIC 3199
Country 142338 0
Australia
Phone 142338 0
+61 412 326 883
Fax 142338 0
Email 142338 0
[email protected]
Contact person for public queries
Name 142339 0
Albert Goikhman
Address 142339 0
Peninsula And Southeast Oncology Suites (PASO), Frankston Private Hospital, Suite 7, Level 3, 5 Susono Way Frankston, VIC 3199
Country 142339 0
Australia
Phone 142339 0
+61 03 9781 5244
Fax 142339 0
Email 142339 0
[email protected]
Contact person for scientific queries
Name 142340 0
Jennifer MacDiarmid
Address 142340 0
EnGeneIC, Building 53, Level 4, 11 Julius Avenue, North Ryde, Sydney, NSW 2113
Country 142340 0
Australia
Phone 142340 0
+61 02 9420 5833
Fax 142340 0
Email 142340 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: For reasons of confidentiality



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
No additional documents have been identified.