To study the Safety, Tolerability and Tumour Response when treated with drug Tigilanol Tiglate administered intratumourally in Patients with Head and Neck Squamous Cell Carcinoma.
- Conditions
- Health Condition 1: C00-C14- Malignant neoplasms of lip, oral cavity and pharynx
- Registration Number
- CTRI/2019/11/022032
- Lead Sponsor
- QBiotics Group Limited
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Other (Terminated)
- Sex
- Not specified
- Target Recruitment
- 13
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 (intratumoural) 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 109/L, and platelets >= 100 x 109/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.
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/ ImlygicTM, 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. Any 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 treat
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To assess the safety and tolerability of tigilanol tiglate when administered as a single intratumoural (IT) dose (at escalating cohorts of dose levels) to patients with HNSCC.Timepoint: Day 1, 3, 7, 14, 21
- Secondary Outcome Measures
Name Time Method To assess the safety and tolerability of tigilanol tiglate when administered as repeat dose intratumoural (IT) injections to patients with HNSCC;To determine the maximum tolerated dose (MTD) level and recommended dose level of tigilanol tiglate;To evaluate the effects of tigilanol tiglate on HNSCC tumours;To evaluate target and non-target tumour response using modified RECIST criteria and volumetric assessment; and To characterise the pharmacokinetic (PK) profile of intratumoural (IT) administered tigilanol tiglate in HNSCC.Timepoint: Day 21