Phase I Dose-Escalation Extension Study to Determine the Safety and Tolerability of Intratumoural Injection(s) of EBC-46
QBiotics Limited
15 participants
Mar 24, 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 they have already participated in the preceding study (QB46C-H01), are aged 18 years or more and have been diagnosed with a cutaneous, subcutaneous, head and neck*, or nodal tumour. *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 an EBC-46 injection(s) directly into a tumour(s). This will occur in the form of consecutive treatment periods, at least a week apart. 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. Participants will be monitored for 3 weeks following each EBC-46 injection in order to evaluate safety, tolerability and tumour response. Treatments will continue until disease progression or intolerance presents. 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 Criteria28
- A patient will be eligible for study participation in the extension study if the patient
- meets all of the following criteria:
- 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;
- 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;
- Patient is able to commence another QB46C-H02 treatment period (i.e. be dosed) within 3.5 months of their last treatment;
- 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;
- 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 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.
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2;
- Has a life expectancy of more than 12 weeks;
- 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;
- 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 urine 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 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 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, other than EBC-46, 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 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;
- 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 human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C infection;
- Patients are pregnant as the effects of EBC-46 on congenital development 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;
- Expected major surgical procedure during the study.
Interested in this trial?
Get notified about updates and connect with the research team.
Interventions
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.
Locations(5)
View Full Details on ANZCTR
For the most up-to-date information, visit the official listing.
ACTRN12614001207606