ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12619000385145

Ethics application status

Approved

Date submitted

26/02/2019

Date registered

12/03/2019

Date last updated

14/10/2022

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]

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

Advanced Cancer (Solid Tumours)

Condition category

Condition code

Cancer

Pancreatic

Cancer

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 enrol 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 two doses administered 30 minutes apart, the first a combination E-EDV-D682/GC followed by a dose of single agent E-EDV-D682. The 2 doses will be given twice per week for the first 2 weeks (8 doses). After which E-EDV-D682/GC and E-EDV-D682, will be administered weekly for 2 further weeks (4 doses) (12 doses over 4 weeks). Week 5 is treatment free, but tumour burden will be radiologically re-evaluated in accordance with iRECIST to determine treatment response.
Subsequent cycles will follow a weekly dosing schedule, where the same 2 doses, E-EDV-D682/GC followed 30 minutes after completion by E-EDV-D682, will be administered weekly for 4 weeks (8 doses). Following each 4-week treatment period is a treatment free week in which tumour burden is radiologically re-assessed (Week 5).

In order to foster tolerance & minimise potential infusion related reactions, the first dose of combination E-EDV-D682/GC at Cycle 1, will be given at a reduced dose level of 2.5 x 10^9. Subsequent doses (Doses 3, 5, 7, 9 and 11) will then be escalated incrementally until the target dose level, 8 x 10^9, is attained at Cycle 1, Dose 11.

Single agent E-EDV-D682 will commence at a starting dose of 2 x 10^9 at Cycle 1, Dose 2, escalating to a maximum dose level of 7 x 10^9 by Cycle 1, Dose 12. All subsequent cycles of both the combination and E-EDV-D682 alone will be administered at the maximum dose levels attained in Cycle 1.

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 enrolment. 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]

Treatment: Drugs

Comparator / control treatment

No control group.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

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]

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]

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]

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]

Assess overall survival (OS) in subjects with advanced pancreatic cancer and other solid tumours when administered E-EDV-D682 with EDV-GC.

Timepoint [3]

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]

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]

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.
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

No limit

Sex

Both males and females

Can healthy volunteers participate?

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

Stopped early

Data analysis

Data collected is being analysed

Reason for early stopping/withdrawal

Participant recruitment difficulties

Date of first participant enrolment

Anticipated

Actual

4/03/2019

Date of last participant enrolment

Anticipated

31/12/2021

Actual

11/03/2022

Date of last data collection

Anticipated

31/10/2022

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

NSW,VIC

Recruitment hospital [1]

Peninsula Oncology Centre - Frankston

Recruitment hospital [2]

Sydney Adventist Hospital - Wahroonga

Recruitment postcode(s) [1]

3199 - Frankston

Recruitment postcode(s) [2]

2076 - Wahroonga

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

EnGeneIC Pty Limited

Address [1]

Building 2/25 Sirius Rd.
Lane Cove West
NSW 2066

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Limited Human Research Ethics Committee D (00444)

Ethics committee address [1]

129 Glen Osmond Road 
Eastwood
SA 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

28/11/2018

Approval date [1]

04/02/2019

Ethics approval number [1]

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 enrol in this trial if you are aged 18 years old or older 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 5-week cycles. The treatments are prepared in a syringe and administered into a vein (intravenous), over a period of 20 minutes using a special pump. Two doses of the treatment are given twice per week for the first 2 weeks, followed by weekly treatment for a further two weeks, with a treatment free week where a CT or MRI scanning is performed to evaluate the tumours response to treatment (Week 5). 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

A/Prof Vinod Ganju

Address

Peninsula and Southeast Oncology Suite 7, Level 3 North Building, Frankston Private Hospital, 5 Susono Way, Frankston VIC 3199

Country

Australia

Phone

+61-3-9781-5244

Fax

office@paso.com.au

Contact person for public queries

Name

Albert Goikhman

Address

Peninsula and Southeast Oncology Suite 7, Level 3 North Building, Frankston Private Hospital, 5 Susono Way, Frankston VIC 3199

Country

Australia

Phone

+61-3-8572-2429

Fax

office@paso.com.au

Contact person for scientific queries

Name

Jennifer MacDiarmid

Address

EnGeneIC Pty Limited
Building 2/25 Sirius Rd.
Lane Cove West,
NSW 2066

Country

Australia

Phone

+61-2-9420-5833

Fax

jmacdiarmid@engeneic.com

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided 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

Source	Title	Year of Publication	DOI
Embase	Update on glioma biotechnology.	2020	https://dx.doi.org/10.1016/j.clineuro.2020.106075
Embase	Phase I/IIa Trial in Advanced Pancreatic Ductal Adenocarcinoma Treated with Cytotoxic Drug-Packaged, EGFR-Targeted Nanocells and Glycolipid-Packaged Nanocells.	2024	https://dx.doi.org/10.1158/1078-0432.CCR-23-1821

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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