Please note that the ANZCTR website will be unavailable from 1pm until 2pm (AEST) on Wednesday 29th May for website maintenance. Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000385145
Ethics application status
Approved
Date submitted
26/02/2019
Date registered
12/03/2019
Date last updated
12/03/2019
Date data sharing statement initially provided
12/03/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
A study of EnGeneIC Dream Vectors (EDV's) packaged with the chemotherapy, E-EDV-D682 given simultaneously as non-targeted EDVs carrying an immune enhancer called EDV-GC, in participants with advanced pancreatic and other cancers whose disease has progressed after one or two treatment regimes, or where other standard therapies are not appropriate.
Scientific title
A Phase I/IIa Study of EGFR-Targeted EDVTMs Carrying the Cytotoxic Drug PNU-159682 (E-EDV-D682) with Concurrent Immunomodulatory Adjuvant Non-Targeted EDVs carrying an immunomodulator (EDV-GC) in (i) Cohort 1, Subjects with Advanced Pancreatic Cancer and (ii) Cohort 2, Subjects with other EGFR Expressing Solid Tumours, who have Failed First or Second-line Therapy or where other Standard Therapies are not Appropriate.
Secondary ID [1] 297385 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The Carolyn Trial / ENG9
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pancreatic Cancer 311538 0
Advanced Cancer (Solid Tumours) 311539 0
Condition category
Condition code
Cancer 310176 310176 0 0
Pancreatic
Cancer 310177 310177 0 0
Any cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an open-label, Phase I/IIa study of EGFR-targeted EDVs containing the cytotoxic drug PNU-159682 (E-EDV-D682), which is administered intravenously (IV) in combination with immunomodulatory EDV-GC in subjects with advanced pancreatic cancer and other EGFR expressing solid tumours who have failed first or second line therapy, or where other standard therapies are not appropriate.

The Phase I component of the study will enroll 5 patients per cohort (5 patients with advanced pancreatic and 5 patients with other EGFR expressing solid tumours), to evaluate the safety and tolerability of the combination of E-EDV-D682 with adjuvant EDV-GC.
The first treatment cycle for both cohorts (pancreatic patients and participants with other solid tumours), is identical and will comprise of bi-weekly doses for 2 weeks, followed by a further 5 doses administered weekly (a total of 9 doses over 7 weeks). In week 8, tumour burden will be radiologically re-evaluated in accordance with iRECIST to determine treatment response.

Subsequent cycles will consist of weekly doses for 7 weeks. Following each 7-week treatment period is a treatment free week in which tumour burden is radiologically re-assessed (Week 8).

In order to foster tolerance & minimise potential infusion related reactions, the first dose of E-EDV-D682 at Cycle 1, will be given at a reduced dose level of 2x10^9. Subsequent doses (Doses 2-9) will then be escalated incrementally until the target dose level, 5 x 10^9, is attained at Cycle 1, Dose 7.

Concurrent EDV-GC will commence at a starting dose of 1x10^8, escalating to a maximum dose level of 5x10^8 by Cycle 1, Dose 7. All subsequent cycles will be administered at the maximum dose level attained at Cycle 1, Dose 7.

Participants may continue to receive investigational medicinal product whilst they continue to derive clinical benefit with no prohibitive toxicity, or until the subject becomes intolerant to the study medication, the subject withdraws consent, or at the discretion of the Investigator if it is felt to be in the best interests of the participant to withdraw.

Post-review by the Safety Monitoring Board and authorization by said committee, the Phase IIa component (dose expansion) will open to enrollment. Up to an additional 35 patients/cohort will be recruited to further evaluate the safety and anti-tumour efficacy of the combination of E-EDV-D682 and EDV-GC (E-EDV-D682/GC) as per the schedule outlined.
Intervention code [1] 313640 0
Treatment: Drugs
Comparator / control treatment
No control group.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319244 0
Assess the safety and tolerability of E-EDV-D682 with EDV-GC in subjects with advanced pancreatic cancer and other EGFR expressing solid tumours who have failed first or second line therapy or where other standard therapies are not appropriate.
Timepoint [1] 319244 0
Safety assessment will involve recording the incidence of Adverse Events (AEs) and clinically significant changes in vital signs and clinical laboratory tests. AE's and vital signs will be assessed pre-dose and then at 1, 2 and 3 hours post-dose infusion for all doses and at the safety withdrawal visit 30-35 days post-final dose.

The very common side effects reported are:
• Chills and shaking (rigors)
• Fever including night sweats
• Abnormalities of liver tests
• Fatigue and lethargy
• Nausea

The common side effects reported are:
• Abnormalities of electrolyte tests
• Headache
• Pain or discomfort at the site of the cancer
• Breathless
• Muscular weakness/aches

A designated Safety Review Committee will assess if any reported adverse event including Serious Adverse Events (SAE's) and Suspected Unexpected Serious Adverse Reactions (SUSAR's) are attributable to the study treatment and fulfill the protocol defined criteria of a Dose Limiting Toxicity (DLT).

Participants will be assessed for DLTs after the first 50 days of treatment. and will include the first 5 patients enrolled in each cohort. In the case of missed doses, the DLT evaluable period will be extended by 7 days for each missed dose so that a DLT evaluable subject is defined as, having received 9 doses and been evaluated for a minimum of 7 days following each dose.
Primary outcome [2] 319245 0
Assess anti-tumour response in subjects with advanced pancreatic cancer and other EGFR expressing solid tumours when administered E-EDV-D682 with EDV-GC.
Timepoint [2] 319245 0
Evidence of anti-tumour activity will be assessed radiologically, and response graded according to iRECIST criteria. The overall response for each subject will be recorded at Week 8 of every cycle of treatment for the duration of treatment. Results for best overall response will be presented for individual participants and for the whole cohort, or relevant subsets, if applicable using frequency counts and percentages.
Primary outcome [3] 319246 0
Assess overall survival (OS) in subjects with advanced pancreatic cancer and other solid tumours when administered E-EDV-D682 with EDV-GC.
Timepoint [3] 319246 0
Survival will be presented as months following administration of Dose 1 for individual subjects, and overall or for relevant subsets if applicable. Survival will continue to be monitored for the duration of the long term follow-up (every 3 months from the safety follow-up visit, for a period of 12 months, and then for the extent of the patients survival). Kaplan Meier curves will be utilised to determine percentage and median survival. There is no control arm for this study. Survival will be compared to historic survival data for individual tumour types.
Secondary outcome [1] 367408 0
Exploratory objective: Assess biomarkers for response such as cellular immune response in patients with advanced pancreatic cancer and other EGFR expressing solid tumours administered E-EDV-D682 with adjuvant EDV-GC (E-EDV-D682/GC).
Timepoint [1] 367408 0
Blood samples will be acquired at scheduled time-points for the duration the patient receives E-EDV-D682/EDV-GC for biomarker analysis.

Eligibility
Key inclusion criteria
1. Eastern Cooperative Oncology Group (ECOG) performance score of 0-1.
2. Life expectancy greater than or equal to 3 months
3. Histologically or cytologically confirmed pancreatic cancer or other solid tumours known to express EGFR including, but not limited to, kidney cancer (renal cell adenocarcinoma), melanoma, bladder cancer, colorectal cancer, non-small cell lung cancer (NSCLC) and head and neck cancer.
4. Measurable disease per iRECIST criteria.
5. Must be able to undergo CT or MRI (+/- PET) evaluation.
6. Available archived primary or metastatic neoplastic tumour tissue available for EGFR expression staining, if not already performed as standard of care.
7. Adequate haematological function.
8. Adequate renal function
9. Adequate hepatic function
11. Adequate cardiac function with LVEF greater than or equal to 50% at baseline.
12. Serum phosphate levels within normal range (2.1-4.1 mg/dL) at baseline.
13. Cortisol levels within normal range, in accordance with hospital accredited laboratory reference range.

Minimum age
18 Years
Maximum age
75 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Significant pericardial effusions, pleural effusions or ascites.
2. Concurrent unstable diabetes mellitus or other contraindications for the use of corticosteroids.
3. Subject has experienced 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 > 160 mmHg or diastolic > 100 mmHg), or cardiac arrhythmias requiring anti-arrhythmic therapy.
4. Clinically significant electrocardiogram (ECG) changes at enrolment which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome.
5. Known to be human immunodeficiency virus (HIV), hepatitis B surface antigen or hepatitis C positive; or with a history of chronic active hepatitis or cirrhosis.
6. History of uncontrolled arterial or venous thrombosis. Subjects with a history of arterial or venous thrombosis are eligible if the subject is controlled on low dose molecular weight heparins or low dose aspirin.
7. Active or uncontrolled severe infection.
8. Previous or current primary malignancies at other sites within last 2 years, except:
- In situ carcinoma of the cervix.
- Adequately treated basal cell or squamous cell carcinoma of the skin.
9. Received the following procedures within 28 days prior to receiving their first dose (or has not recovered from the toxic effects of such therapy) including:
- other investigational therapy
- radiotherapy
- any major surgery.
10. Prior other therapies or procedures prior to receiving their first dose:
- Anticoagulation therapy (within 7 days of Study Day 1), except low molecular weight heparins or low dose aspirin.
- QTc interval prolonging medicines should be reviewed and where possible their use should be minimized and alternate medicines that are not QTc interval prolonging considered as substitutes.
11. Known allergy/hypersensitivity to investigational components or excipients (trehalose, monoclonal antibody infusions, interferon therapy, or ciprofloxacin HCl (or other quinolones).
12. Female who is pregnant or breastfeeding.
13. Subject 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
Due to the small number of subjects to be enrolled findings will be presented in a descriptive manner with no formal statistical comparisons performed. Data will be presented for individual subjects. Where feasible, continuous data will be summarised by the following descriptive statistics: n (number of observations), mean, standard deviation, median, minimum, maximum. Categorical data will be summarised by frequencies and percentages.

Recruitment
Recruitment status
Recruiting
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)
VIC
Recruitment hospital [1] 13259 0
Peninsula Oncology Centre - Frankston
Recruitment postcode(s) [1] 25822 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 302092 0
Commercial sector/Industry
Name [1] 302092 0
EnGeneIC Pty Limited
Address [1] 302092 0
Building 2/25 Sirius Rd.
Lane Cove West
NSW 2066
Country [1] 302092 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
EnGeneIC Pty Limited
Address
Building 2/25 Sirius Rd.
Lane Cove West
NSW 2066
Country
Australia
Secondary sponsor category [1] 301913 0
None
Name [1] 301913 0
Address [1] 301913 0
Country [1] 301913 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302771 0
Bellberry Limited Human Research Ethics Committee D (00444)
Ethics committee address [1] 302771 0
129 Glen Osmond Road
Eastwood
SA 5063
Ethics committee country [1] 302771 0
Australia
Date submitted for ethics approval [1] 302771 0
28/11/2018
Approval date [1] 302771 0
04/02/2019
Ethics approval number [1] 302771 0
2018-11-1008

Summary
Brief summary
The primary purpose of this trial is to evaluate the safety and efficacy of a combination treatment consisting of EDV's packaged with a chemotherapeutic targeted to cancer cells and an adjuvant therapy that is designed to boost the bodies own immune system to fight the cancer.
In Phase I the study will enrol 5 evaluable patients per cohort.
In Phase IIa the study, will enrol up to an additional 35 evaluable patients per cohort.
Therefore up to 40 evaluable subjects per cohort will be enrolled in the study.

Who is it for?
You may be eligible to enroll in this trial if you are aged 18 to 75 years old and have either advanced pancreatic cancer or any solid tumour that has been treated with at least one prior treatment regime or where other standard therapies are not appropriate.

Study details
All participants enrolled in this trial will receive combination treatment with the following:
1. The EnGeneIC Dream Vector(TM) (EDV(TM)). The EDVs are very small particles known as nanocells, which are made from Salmonella bacteria. The type of Salmonella is one that does not cause disease. The EDV is the delivery vehicle used to transport the study drug directly to the site of the cancer.
2. The Cancer Treatment. The study drug is a type of chemotherapy. The study drug is packaged inside the EDVs (E-EDV-D682) and is targeted directly to the site of the tumour, rather than the body’s healthy cells and tissues. The EDVs will also be packaged with another substance that is designed to boost the immune system, called EDV-GC.
3. Bispecific antibody. The EDV delivery system works in 2 ways, as well as carrying the study drug, the EDV surface is also coated with a bispecific antibody. A bispecific antibody is two antibodies linked together, such that one can attach to the EDV and the other to cancer cells. Once attached, the EDVs are taken up inside the cancer cells, and the study drug is delivered directly inside the cell itself, causing the cancer cell to die.

Treatment will be administered in 8-week cycles. The treatment is combined in a syringe and administered in to a vein (intravenous), over a period of 20 minutes using a special pump. One dose of the treatment is given each week for the first 7 weeks, followed by a treatment free week where a CT or MRI scanning is performed to evaluate the tumours response to treatment (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 patients disease continues to grow.

It is hoped that the findings from this trial will provide information on whether E-EDV-D682 and EDV-GC treatment may be safe and effective for the treatment of otherwise incurable pancreatic and other advanced solid tumours.
Trial website
www.paso.com.au/clinical-trials/current-trials/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 44090 0
A/Prof Vinod Ganju
Address 44090 0
Peninsula and Southeast Oncology Suite 7, Level 3 North Building, Frankston Private Hospital, 5 Susono Way, Frankston VIC 3199
Country 44090 0
Australia
Phone 44090 0
+61-3-9781-5244
Fax 44090 0
Email 44090 0
office@paso.com.au
Contact person for public queries
Name 44091 0
Mr Albert Goikhman
Address 44091 0
Peninsula and Southeast Oncology Suite 7, Level 3 North Building, Frankston Private Hospital, 5 Susono Way, Frankston VIC 3199
Country 44091 0
Australia
Phone 44091 0
+61-3-8572-2429
Fax 44091 0
Email 44091 0
office@paso.com.au
Contact person for scientific queries
Name 44092 0
Dr Jennifer MacDiarmid
Address 44092 0
EnGeneIC Pty Limited
Building 2/25 Sirius Rd.
Lane Cove West,
NSW 2066
Country 44092 0
Australia
Phone 44092 0
+61-2-9420-5833
Fax 44092 0
Email 44092 0
jmacdiarmid@engeneic.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
For reasons of confidentiality.
What supporting documents are/will be available?
No other documents available
Summary results
No Results