Phase I Dose-Escalation Extension Study to Determine the Safety and Tolerability of Intratumoural Injection(s) of EBC-46

• Register: ANZCTR
• Last refreshed on: 13 January 2020
• Main ID: ACTRN12614001207606
• Date of registration: 17/11/2014
• Prospective Registration: Yes
• Primary sponsor: QBiotics Limited
• Public title: Phase I Dose-Escalation Extension Study to Determine the Safety and Tolerability of Intratumoural Injection(s) of EBC-46
• Scientific title: Phase I Dose-Escalation Extension Study to Determine the Safety and Tolerability of Intratumoural Injection(s) of EBC-46
• Date of first enrolment: 24/03/2015
• Target sample size: 15
• Recruitment status: Completed
• URL: https://anzctr.org.au/ACTRN12614001207606.aspx
• Study type: Interventional
• Study design: Purpose: Treatment; Allocation: Non-randomised trial; Masking: Open (masking not used);Assignment: Single group;Type of endpoint: Safety;
• Phase: Phase 1

Countries of recruitment

Australia, New Zealand

Contacts

• Name: Dr Daina Vanags

• Name: Mr Daniel Swart

Key inclusion & exclusion criteria

Inclusion criteria: A patient will be eligible for study participation in the extension study if the patient
meets all of the following criteria:
1. Patient has either completed the QB46C-H01 protocol, or has been enrolled in QB46C-H02, and, in the opinion of the Investigator, might benefit from continued treatment with EBC-46;
2. Patient is able to commence the extension study (i.e. be dosed on Day 1) within 3.5 months of the last visit of the QB46C-H01 protocol;
3. Patient is able to commence another QB46C-H02 treatment period (i.e. be dosed) within 3.5 months of their last treatment;
4. Previously treated tumour(s) have a complete covering of skin (“healed”) or at least evidence of healing (e.g., reduction in size of any wound) or stabilisation;
5. Adult (18 years or older) with histologically or cytologically confirmed tumours;
6. 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 refused standard therapy despite 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.
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
8. Has a life expectancy of more than 12 weeks;
9. Haemoglobin greater than or equal to 90 g/L, neutrophils greater than or equal to 1.5 x 10^9 L, platelets greater than or equal to 100 x 10^9 L;
10. Total bilirubin less than or equal to 1.5 x upper limit of normal;
11. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than or equal to 3 x upper limit of normal;
12. Plasma creatinine less than or equal to 1.5 x upper limit of normal;
13. International Normalized Ratio (INR) and APTT less than or equal to 1.5 x upper limit of normal;
14. Negative urine pregnancy test; and
15. 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 the last treatment day.
*except for pharyngeal, laryngeal and tongue base tumours and those tumours in the anterior neck (from posterior border of sternocleidomastoid on each side).
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, other than EBC-46, 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 V4.03] Grade less than or equal to 1) except for fatigue (less than or equal to Grade 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 human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection;
14. Patients are pregnant as the effects of EBC-46 on congenital development 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. Expected major surgical procedure during the study.

Age minimum: 18 Years
Age maximum: No limit
Gender: Both males and females

Health Condition(s) or Problem(s) studied

Cancer - Head and neck

Cancer - Non melanoma skin cancer

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);
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)

Cancer - Malignant melanoma

Intervention(s)

This is a multi-centre, single-agent, open-label, Phase I dose-escalation extension study of EBC-46 to evaluate the safety and tolerability of repeated administrations of EBC-46 in patients who have successfully completed the main protocol (QB46C-H01, ANZCTR Trial ID: ACTRN12614000685617).
Patients will undergo a screening visit up to 3 months after completing the QB46C-H01 study. Treatment will be a single dose administered via intratumoural injection with safety monitoring for 21 days. Patients will be required to return for follow up assessments on Day 2, Day 8 (plus or minus 1 day), Day 15 (plus or minus 1 day) and Day 22 (plus or minus 1 day). Treatments will continue no sooner than 1 week since the last injection and will conclude when disease progression or intolerance presents.
Patients will initially receive the same dose level as they received in QB46C-H01 (if tolerated) or lower (if not tolerated or there is less tumour mass requiring dosing). Lower doses will be considered for patients who experienced a dose limiting toxicity (DLT) or Grade > 3 adverse event (AE) in the QB46C-H01 study or if the tumour burden requires less EBC-46.
The dose may be escalated to a higher level if that higher dose level has been demonstrated to be well-tolerated in the QB46C-H01 study (based on the incidence and severity of AEs and DLTs in the QB46C-H01 study) as determined by the Safety Review Committee.

Primary Outcome(s)

To determine the safety and tolerability of EBC-46 when administered via intratumoural injection(s). This will be determined by evaluation of the safety parameters collected during the study, 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.[Between Day 1 and Day 22 for each treatment. ]

Secondary Outcome(s)

The effects of EBC-46 on tumour size will be evaluated by using 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. Callipers will be used to estimate tumour volume, and to estimate tumour response based on tumour volume relative to baseline measurements, where possible. [Calliper measurements, where possible, will be taken at baseline and weekly to Day 22 for each treatment period. ]

Secondary ID(s)

QB46C-H02

Source(s) of Monetary Support

QBiotics Limited

Ethics review

Status: Approved
Approval date:
Contact:

Central Health and Disability Ethics Committee

Status: Approved
Approval date:
Contact:

The Alfred Health Human Ethics Committee

Results

• Results available: Yes
• Date Posted: 11/12/2019
• Date Completed: 14/06/2017