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Trial registered on ANZCTR


Registration number
ACTRN12614000685617
Ethics application status
Approved
Date submitted
23/06/2014
Date registered
27/06/2014
Date last updated
11/12/2019
Date data sharing statement initially provided
11/12/2019
Date results provided
11/12/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Phase I Dose-Escalation Study to Determine the Safety and Tolerability of an Intratumoural Injection of EBC-46
Scientific title
Phase I Dose-Escalation Study to Determine the Safety and Tolerability of an Intratumoural Injection of EBC-46
Secondary ID [1] 284858 0
QB46C-H01
Universal Trial Number (UTN)
Trial acronym
Linked study record
ACTRN12614001207606

Health condition
Health condition(s) or problem(s) studied:
Cutaneous, subcutaneous, head and neck*, or nodal tumours
*except for pharyngeal, laryngeal and tongue base tumours and those tumours in the anterior neck (from posterior border of sternocleidomastoid on each side) 292256 0
Condition category
Condition code
Cancer 292599 292599 0 0
Head and neck
Cancer 292600 292600 0 0
Malignant melanoma
Cancer 292601 292601 0 0
Non melanoma skin cancer

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a multi-centre, single-agent, open-label, Phase I accelerated dose escalation study of EBC-46. Initially, single-patient cohorts will be evaluated, with the first dose being 0.06 mg/m2. Once adverse-event specific triggers are seen during this stage, the study will revert to a standard 3+3 oncology design, with dose escalation also being based on the incidence and severity of adverse events. Treatment will be a single dose administered via intratumoural injection with weekly monitoring for 21 days.
The study will conclude when either a Maximum Tolerated Dose (MTD) is identified, or the Sponsor or Safety Review Committee (SRC) decide that the study should be terminated.
Intervention code [1] 289659 0
Treatment: Drugs
Comparator / control treatment
Nil
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292451 0
To determine the safety and tolerability of EBC-46 when administered via intratumoural injection. This will be determined using the safety parameters collected during the trial, including: -Laboratory tests; -12-lead electrocardiogram (ECG); -AEs/SAEs (toxicities will be assessed using the CTCAE V4.03); -Local injection site reactions; -Vital signs; and -Wound healing.
Timepoint [1] 292451 0
This will be between Day 1 and Day 8 to allow for dose escalation, however safety will be evaluated up to Day 22.
Secondary outcome [1] 308982 0
To determine the plasma pharmacokinetics (PK) of EBC-46 when administered once via intratumoural injection. Analysis will be completed using a validated LC-MS/MS method.
Timepoint [1] 308982 0
PK time points on Day 1 at pre-dose, 5, 15, 30 mins and 1, 2, 4, 6, 8 and 24 hours post-dose.
Secondary outcome [2] 308983 0
The effects of EBC-46 on tumour size will be evaluated by using computed tomography (CT) and calliper measurements (where possible). RECIST 1.1 guidelines will be applied to evaluate response and change in treated (up to three target tumours) and non-treated (up to five non-target) tumour size(s). Volumetric analysis will also be conducted for target and non-target tumours. CT and callipers (where possible) will be used to estimate tumour volume, and to estimate tumour response based on tumour volume relative to baseline measurements.
Timepoint [2] 308983 0
Calliper measurements will be taken at baseline and weekly to Day 22., where possible. CT scan will be taken at baseline and on Day 22.
Secondary outcome [3] 308984 0
Exploratory objective:
To determine whether the action of EBC-46 can be characterised through biomarker analysis of blood and/or tumour tissue collected at intervals following dosing.
Timepoint [3] 308984 0
Blood biomarkers will be collected on Day 1 at pre-dose, 5, 15, 30 mins and 1, 2, 4, 6, 8 and 24 hours post dose as well as Days 8, 15 and 22. For consenting patients in dose expansion (3+3) and characterisation cohorts, a FNA/Tru-Cut/Punch biopsy will be taken at baseline and 6 hours post dose on Day 1 of the study.

Eligibility
Key inclusion criteria
A patient will be eligible for study participation if the patient meets all of the following criteria:
1. Able to understand and sign an informed consent document;
2. Adult (18 years or older) with histologically or cytologically confirmed tumours;
3. Has cutaneous, subcutaneous, head and neck*, or nodal tumours:
- refractory to at least one round of conventional therapy; or
- for whom there is no standard therapy; or
- has declined standard therapy after appropriate counselling (this will be documented); or
- that are awaiting therapy or are explicitly being monitored with the aim of delaying therapy.
These may include but are not limited to:
i) Squamous cell carcinoma of the head and neck;
ii) Squamous cell carcinoma of the skin;
iii) Merkel cell tumours of the skin;
iv) Malignant melanoma;
v) Skin metastases.
4. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
5. Has a life expectancy of more than 12 weeks;
6. Has disease that is measurable so that response to therapy can be assessed. This is defined as tumours to be treated that can be accurately measured in at least two dimensions with conventional techniques (computed tomography [CT] and, where possible, callipers); and, except for the Local Effects Cohort, determined to be at least sufficient in total volume to allow the volume of Investigational Product (IP) for that dose level to be delivered. Up to three tumours can be treated;
7. Haemoglobin greater than or equal to 9.0 g/ dL, neutrophils greater than or equal to 1.5 x 10^9 L, platelets greater than or equal to 100 x 10^9 L;
8. Total bilirubin less than or equal to 1.5 x upper limit of normal;
9. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than or equal to 3 x upper limit of normal;
10. Plasma creatinine less than or equal to 1.5 x upper limit of normal;
11. International Normalized Ratio (INR) and APTT less than or equal to 1.5 x upper limit of normal;
12. Negative serum pregnancy test; and
13. Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following Day 1.
*except for pharyngeal, laryngeal and tongue base tumours and those tumours in the anterior neck (from posterior border of sternocleidomastoid on each side)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
A patient will be excluded from the study if the patient meets any of the following criteria:
1. Has treatment with any immunotherapy, biological therapy, or chemotherapy or major surgery within three weeks prior to study treatment (six weeks for nitrosoureas or mitomycin C);
2. Has treatment with any investigational agent for treatment of cancer or related comorbidity within four weeks prior to study treatment or during enrolment in this Protocol;
3. Has had radiation therapy to a visceral organ or tumours within three weeks prior to study treatment;
4. Has known, uncontrolled, CNS metastases;
5. Has a history of significant tumour bleeding in the target (to be treated) tumour(s);
6. Has a target tumour mass(es) immediately adjacent to, or with infiltration into, major arteries, veins or vessels;
7. Patients with a bleeding diathesis or coagulopathy that would make intratumoural injection or biopsy unsafe; patients on therapeutic anticoagulation or anti-platelet agents (such as clopidogrel) are excluded. Prophylactic doses of low molecular weight heparins or low-dose aspirin (less than or equal to 150 mg daily) is allowed;
8. Having not recovered from the toxic effects of previous therapy (Common Terminology Criteria for AEs [CTCAE 4.03] Grade less than or equal to 1) except for fatigue (Grade less than or equal to 2) due to radiation treatment and alopecia;
9. Myocardial infarction, unstable angina pectoris, cerebrovascular accident, pulmonary embolism, uncontrolled congestive heart failure, cardiac arrhythmia (except for controlled atrial fibrillation), arterial thrombosis or transient ischemic attack within the last six months;
10. Significant cardiac comorbidity or poorly controlled hypertension (>150/100 mg Hg) despite optimal medical therapy;
11. Anti-tumour vaccine therapy within six weeks of study treatment;
12. History of allergic reactions attributed to compounds of similar chemical or biologic composition to agent(s) or other agents used in study;
13. Has uncontrolled disease associated with known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection;
14. Patients are pregnant or nursing as the effects of EBC-46 on congenital development and nursing infants are unknown;
15. If, in the opinion of the Investigator, the patient is an inappropriate candidate for the study;
16. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements;
17. Prior treatment with EBC-46 in this study; and
18. Expected surgical procedure during the study.

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)
Allocation is not concealed
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
Other
Other design features
Accelerated trial design (single patient cohorts) and subsequently 3+3 oncology design.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
Descriptive statistics

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
27/10/2014
Actual
13/02/2015
Date of last participant enrolment
Anticipated
31/01/2017
Actual
1/06/2017
Date of last data collection
Anticipated
Actual
27/06/2017
Sample size
Target
15
Accrual to date
Final
22
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 2660 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 2661 0
The Alfred - Prahran
Recruitment hospital [3] 2662 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [4] 2663 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 8324 0
2170 - Liverpool
Recruitment postcode(s) [2] 8325 0
3004 - Melbourne
Recruitment postcode(s) [3] 8326 0
5042 - Bedford Park
Recruitment postcode(s) [4] 8327 0
4102 - Woolloongabba
Recruitment outside Australia
Country [1] 8507 0
New Zealand
State/province [1] 8507 0
Mount Cook, Wellington, 6021

Funding & Sponsors
Funding source category [1] 289471 0
Commercial sector/Industry
Name [1] 289471 0
QBiotics Limited
Country [1] 289471 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
QBiotics Limited
Address
7 Penda Street, Yungaburra, Queensland, Australia, 4884
Country
Australia
Secondary sponsor category [1] 288158 0
None
Name [1] 288158 0
Nil
Address [1] 288158 0
Nil
Country [1] 288158 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291228 0
The Alfred Health Human Ethics Committee
Ethics committee address [1] 291228 0
Ethics committee country [1] 291228 0
Australia
Date submitted for ethics approval [1] 291228 0
23/06/2014
Approval date [1] 291228 0
27/08/2014
Ethics approval number [1] 291228 0
Ethics committee name [2] 296540 0
Central Health and Disability Ethics Committee
Ethics committee address [2] 296540 0
Ethics committee country [2] 296540 0
New Zealand
Date submitted for ethics approval [2] 296540 0
10/05/2016
Approval date [2] 296540 0
24/06/2016
Ethics approval number [2] 296540 0
Ethics Reference: 16/CEN/60

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

Contacts
Principal investigator
Name 49418 0
Dr Jason Lickliter
Address 49418 0
The Nucleus Network
5th Floor, Burnett Tower, 89 Commercial Road
Melbourne, Victoria 3004
Country 49418 0
Australia
Phone 49418 0
+ 61 3 9076 8892
Fax 49418 0
+ 61 3 9076 8911
Email 49418 0
contactus@nucleusnetwork.com.au
Contact person for public queries
Name 49419 0
Daniel Swart
Address 49419 0
QBiotics Group Limited, 3A/165 Moggill Road, Taringa, Queensland, 4068
Country 49419 0
Australia
Phone 49419 0
+61 7 3870 8933
Fax 49419 0
Email 49419 0
enquiries@qbiotics.com
Contact person for scientific queries
Name 49420 0
Daina Vanags
Address 49420 0
QBiotics Group Limited, 3A/165 Moggill Road, Taringa, Queensland, 4068
Country 49420 0
Australia
Phone 49420 0
+61 7 3870 8933
Fax 49420 0
Email 49420 0
enquiries@qbiotics.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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
SourceTitleYear of PublicationDOI
Dimensions AITigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade2024https://doi.org/10.1136/jitc-2022-006602
N.B. These documents automatically identified may not have been verified by the study sponsor.