Exploratory Phase Ib/IIa Study of Intratumourally Administered Tigilanol Tiglate to Assess Safety, Tolerability and Tumour Response in Patients with Head and Neck Squamous Cell Carcinoma

Phase 1

• Conditions: Head and neck squamous cell carcinoma.; Cancer - Head and neck

• Registration Number: ACTRN12619001407189
• Lead Sponsor: QBiotics Group Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-10-14
• Study Completion: 2021-09-28
• Last Update Posted: 19 April 2022

Recruitment & Eligibility

• Status: Stopped early
• Sex: All
• Target Recruitment: 19

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-c

Study & Design

• Study Type: Interventional
• Study Design: Not specified