None listed
Conditions
Brief summary
This study aims to evaluate the safety, tolerability and signs of efficacy of a new investigational drug called tigilanol tiglate in participants with head and neck cancer. Who is it for? Patients may be eligible to join this study if aged 18 years or more and have been diagnosed with head and neck squamous cell carcinoma. Study details: All participants in this study will receive between one and three tigilanol tiglate injections directly into 1-4 tumours. Tigilanol tiglate 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 previously been tested in humans (see QB46C-H01 - ACTRN12614000685617 and QB46C-H02 - ACTRN12614001207606). Participants will be monitored for at least 3 weeks following tigilanol tiglate 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.
Interventions
This is a multi-centre, single-agent, open-label, Phase Ib/IIa study to evaluate the safety, tolerability and signs of efficacy of tigilanol tiglate when administered as a single or multiple (two or three) intratumoural treatment(s) to patients with head and neck squamous cell carcinoma.
The study consists of 2 stages.
In Stage 1, patient will be enrolled into one of two cohorts at a starting dose level of up to 1.2 mg/m2 body surface area (BSA). A single treatment will be administered to 1 – 4
This is a multi-centre, single-agent, open-label, Phase Ib/IIa study to evaluate the safety, tolerability and signs of efficacy of tigilanol tiglate when administered as a single or multiple (two or three) intratumoural treatment(s) to patients with head and neck squamous cell carcinoma. The study consists of 2 stages. In Stage 1, patient will be enrolled into one of two cohorts at a starting dose level of up to 1.2 mg/m2 body surface area (BSA). A single treatment will be administered to 1 – 4 target tumours via intratumoural injection, followed by monitoring for 21 days. The first cohort, containing patients with a larger combined target tumour volume (~4.0 - 150.0 cm3) which cannot be entirely treated at 50% v/v (0.5 mL dose volume / 1.0 cm3 tumour) at the current dose level (mg/m2 BSA), will be of a standard 3+3 escalation design with dose-escalation being based on the incidence and severity of adverse events and determined by an independent Data Safety Monitoring Board (DSMB). The second cohort, containing patients with a smaller combined target tumour volume (0.1 - ~4.0 cm3) that can be entirely treated at 50% v/v (0.5 mL dose volume / 1.0 cm3 tumour) without reaching the current dose level (mg/m2 BSA), will escalate in dose level based on the first cohort's DSMB results. Following completion of Stage 1, and at the principal investigator's discretion, patients may progress on to Stage 2. In Stage 2 patients that have completed Stage 1 may receive up to two additional treatments, one week apart, to the same target tumour(s) and at the same dose level as in Stage 1. The study will conclude when either a Maximum Tolerated Dose is identified, or the Sponsor and DSMB decide that the study should be terminated.
Sponsors
QBiotics Group Limited
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient will be eligible for study participation (Stage 1 and Stage 2, if applicable) if they meet all of the following criteria: 1. An adult (>= 18 years old); 2. Willing and able to provide written informed consent prior to any protocol-required procedures and comply with all local and study requirements; 3. Resectable or unresectable, histologically or cytologically confirmed HNSCC, accessible and amenable for IT injection, that meets at least one of the following: • refractory to at least one round of conventional therapy; or • no available standard therapy; or • patient declined standard therapy after appropriate counselling (with the decision documented); or • patient awaiting surgery or therapy or is explicitly being monitored with the aim of delaying therapy. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2; 5. Life expectancy more than 12 weeks; 6. Disease that is measurable (i.e., each target tumour >= 2 mm in diameter that can be accurately measured in at least two dimensions) by calliper. Up to 4 measurable target tumours with a maximum combined volume of 150 cm3 and up to 5 non-target tumours to be selected at the discretion of the PI; 7. Selected target tumours that are suitable for biopsy (multiple 2 mm punch sampling) and patient willingness to provide tumour biopsies; 8. Haemoglobin >= 9.0 g/dL, neutrophils >= 1.5 x 10^9/L, and platelets >= 100 x 10^9/L; 9. Total bilirubin =< 1.5 x upper limit of normal (ULN); 10. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 x ULN; 11. Plasma creatinine =< 2.0 x ULN; 12. International Normalised Ratio (INR) and APTT =< 1.5 x ULN; 13. Women of child-bearing potential (i.e., not pre-menarchal, surgically permanently sterile [hysterectomy, bilateral salpingectomy and bilateral oophorectomy], or >= 12 months postmenopausal without an alternative medical cause) must not be pregnant (as demonstrated by negative serum beta-human chorionic gonadotropin [hCG] pregnancy test) and all men must agree to use adequate contraception (i.e., sexual abstinence [only if preferred method of birth control]; oral, intravaginal, or transdermal combined estrogen and progesterone hormonal contraception associated with inhibition of ovulation; oral, injectable, or implantable progesterone-only hormonal contraception associated with inhibition of ovulation; intrauterine device [IUD]; intrauterine hormone-releasing system [IUS]; bilateral tubal occlusion; or only vasectomized sexual partner[s]) prior to study entry, for the duration of study participation, and for 90 days following the last treatment day. Additionally, men must agree to not donate sperm for the duration of study participation or for 90 days following the last treatment day.
Exclusion criteria
A patient will be excluded from the study if they meet any of the following criteria: 1. Target tumours intended for treatment immediately adjacent to, or with infiltration into, major arteries or veins; 2. Target tumours intended for treatment located in an area where post-injection swelling could compromise the airway; 3. Target tumours intended for treatment requiring urgent resection; 4. Participated in any investigational intervention study within 30 days prior to study treatment; 5. Treatment with any anti-cancer treatment (e.g., immunotherapy [e.g., anti-PD-1/L1 inhibitor], biological therapy, chemotherapy, anti-cancer vaccine therapy, oncolytic viral or microbial therapy [e.g., T-VEC/Imlygic(TM), toll-like receptor [TLR] agonists, STING or RIG-1], etc.) other than prior tigilanol tiglate injection as part of this study, within 4 weeks prior to study treatment; 6. Oncology related surgery within 4 weeks prior to study treatment; 7. Any previous surgery in the area of the intended target tumour in proximity of the airway (such that tracking of the injected fluid may be unpredictable and could lead to airway swelling); 8. Any radiation therapy to a visceral organ or tumours within 3 weeks prior to study treatment; 9. Any previous radiation of the intended target tumour in proximity of the airway (such that tracking of the injected fluid may be unpredictable and could lead to airway swelling); 10. Unrecovered to CTCAE version 5 Grade 1 or better from the toxic effects of any previous therapy prior to study enrolment, except for fatigue (Grade =< 2) due to radiation treatment and alopecia (Grade =< 2). Other Grade 2 AEs that are deemed as Grade 2 due to replacement hormonal or steroid therapies may qualify for exception to this criterion with approval of the Medical Monitor; 11. Known, uncontrolled CNS metastasis; 12. History of significant tumour bleeding in the target tumour intended for treatment; 13. Therapeutic anticoagulation or antiplatelet agents (e.g., clopidogrel) (Prophylactic doses of low molecular weight heparins or low dose aspirin [=< 150 mg daily] are allowed) (low molecular weight heparin must be stopped at least 24 hours prior to study treatment); 14. A bleeding diathesis or coagulopathy that would make IT injection or biopsy unsafe; 15. Myocardial infarction, unstable angina pectoris, cerebrovascular accident, pulmonary embolism, uncontrolled congestive heart failure, cardiac arrhythmia (except for controlled atrial fibrillation), arterial thrombosis, or transient ischaemic attack within 6 months prior to study treatment; 16. Significant cardiac comorbidity or uncontrolled hypertension (> 150/100 mmHg), despite optimal medical therapy, that may confound the assessment of safety and tolerability; 17. History of allergic reactions attributed to compounds of similar chemical or biologic composition to tigilanol tiglate or other agents used in this study; 18. Uncontrolled bacterial, viral, or fungal infections requiring systemic therapy, known infection with human immunodeficiency virus (HIV), or active infection with Hepatitis B or Hepatitis C; 19. Pregnant or nursing (the effects of tigilanol tiglate on congenital development and nursing infants are unknown); 20. In the opinion of the PI, the patient is an inappropriate candidate for the study; 21. For consideration when entering Stage 2 - Repeat-Dosing only: Any anti-cancer treatment (e.g., immunotherapy, biological therapy, chemotherapy, anti-cancer vaccine therapy, surgery, etc.) to the target tumour since the previous treatment with tigilanol tiglate; 22. For consideration when entering Stage 2 - Repeat-Dosing only: No unacceptable toxicity to a previous tigilanol tiglate injection.
Outcome results
None listed