Phase I Dose-Escalation Study to Determine the Safety and Tolerability of an Intratumoural Injection of EBC-46
QBiotics Limited
15 participants
Feb 13, 2015
Interventional
Conditions
Summary
This study aims to evaluate the safety and tolerability of a new investigational drug called EBC-46 in participants with cancer. Who is it for? Patients may be eligible to join this study if aged 18 years or more and have been diagnosed with cutaneous, subcutaneous, head and neck* or nodal tumour(s). *except for pharyngeal, laryngeal and tongue base tumours and those tumours in the anterior neck (from posterior border of sternocleidomastoid on each side) Study details: All participants in this study will receive a single EBC-46 injection directly into tumours. EBC-46 may lead to breakdown of tumour blood vessels and recruitment and activation of white blood cells. This leads to rapid tumour cell death. This drug has not previously been tested in humans. Participants will be monitored for 3 weeks following EBC-46 injection in order to evaluate safety, tolerability, tumour response and pharmacokinetics (the action of the body on the drug). The results from this study will be analysed to see if it is worthwhile for this new drug to be tested in future studies involving larger numbers of cancer participants.
Eligibility
Inclusion Criteria25
- A patient will be eligible for study participation if the patient meets all of the following criteria:
- Able to understand and sign an informed consent document;
- Adult (18 years or older) with histologically or cytologically confirmed tumours;
- 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.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
- Has a life expectancy of more than 12 weeks;
- 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;
- 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;
- Total bilirubin less than or equal to 1.5 x upper limit of normal;
- Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than or equal to 3 x upper limit of normal;
- Plasma creatinine less than or equal to 1.5 x upper limit of normal;
- International Normalized Ratio (INR) and APTT less than or equal to 1.5 x upper limit of normal;
- Negative serum pregnancy test; and
- 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)
Exclusion Criteria19
- A patient will be excluded from the study if the patient meets any of the following criteria:
- 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);
- 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;
- Has had radiation therapy to a visceral organ or tumours within three weeks prior to study treatment;
- Has known, uncontrolled, CNS metastases;
- Has a history of significant tumour bleeding in the target (to be treated) tumour(s);
- Has a target tumour mass(es) immediately adjacent to, or with infiltration into, major arteries, veins or vessels;
- 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;
- 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;
- 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;
- Significant cardiac comorbidity or poorly controlled hypertension (>150/100 mg Hg) despite optimal medical therapy;
- Anti-tumour vaccine therapy within six weeks of study treatment;
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to agent(s) or other agents used in study;
- Has uncontrolled disease associated with known human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection;
- Patients are pregnant or nursing as the effects of EBC-46 on congenital development and nursing infants are unknown;
- If, in the opinion of the Investigator, the patient is an inappropriate candidate for the study;
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements;
- Prior treatment with EBC-46 in this study; and
- Expected surgical procedure during the study.
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Interventions
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.
Locations(5)
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ACTRN12614000685617