A Clinical Study to Investigate the Efficacy of Tigilanol Tiglate Directly in Head and Neck Cancer

• ClinicalTrials.gov Identifier: NCT05608876
• Recruitment Status: Recruiting
• First Posted: November 8, 2022
• Last Update Posted: May 31, 2023
• Sponsor: QBiotics Group Limited
• Information provided by (Responsible Party): QBiotics Group Limited

Study Description

Brief Summary:

A Phase II, open label, single arm study to assess the efficacy of intratumoural tigilanol tiglate in various head and neck solid malignancies.

Condition or disease	Intervention/treatment	Phase
Head and Neck Cancer	Drug: Tigilanol Tiglate	Phase 2

Detailed Description:

Primary Objective

1. To evaluate tumour ablation following treatment(s) with intratumoural injections of tigilanol tiglate.

Secondary Objectives

1. To assess the safety and tolerability of intratumoural injections with tigilanol tiglate.
2. To evaluate disease control by assessing time to local disease recurrence from last treatment.
3. To evaluate the tumour recurrence rate at injected tumour sites.
4. To evaluate survival by assessing Progression Free Survival (PFS).

Exploratory Objectives

1. To assess the impact on Quality of Life (QoL).
2. To assess the degree of wound healing after each treatment.
3. To assess the tumour response in injected and non-injected tumours, based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1.
4. To assess the tumour response according to intratumoural Response Evaluation Criteria in Solid Tumours (itRECIST).
5. To assess changes in tumour biomarkers.
6. To assess the tumour microenvironment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 37 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Open label, single arm
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Open Label, Single Arm Study To Assess The Efficacy Of Intratumoral Tigilanol Tiglate In Various Head And Neck Solid Malignancies
• Actual Study Start Date: November 3, 2022
• Estimated Primary Completion Date: August 2025
• Estimated Study Completion Date: October 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: Single Arm, Open Label; Single or multiple Intratumoural injections of tigilanol tiglate at up to a fixed dose of 3.6 mg/m2 (Body Surface Area [BSA]) per treatment.	Drug: Tigilanol Tiglate; Tigilanol tiglate is a novel, short-chain diterpene ester in clinical development for intratumoural treatment of a wide range of solid tumours.; Other Name: EBC-46

Outcome Measures

Primary Outcome Measures :

1. Tumour Response [ Time Frame: 72 weeks ]
   Proportion of participants who have achieved partial or complete ablation of treated tumour(s) and/or tumour segment(s) following injection(s) with tigilanol tiglate.

Secondary Outcome Measures :

1. Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 72 weeks ]
   Total number of Adverse Events (AEs) and Serious Adverse Events (SAEs) and number of AEs and SAEs deemed related to tigilanol tiglate.
2. Disease Control [ Time Frame: 72 weeks ]
   Time from last treatment to recurrence of disease at injection site(s).
3. Local Recurrence Rate at injection site(s) [ Time Frame: 6-, 12-, and 18-months after first treatment. ]
   Percentage of participants with local recurrence at injection site(s) at 6-,12- and 18-months after first treatment.
4. Progression Free Survival (PFS) [ Time Frame: 72 weeks ]
   Progression Free Survival (PFS) based on RECIST v1.1 defined as the length of time between first treatment and the date of the first occurrence of disease progression.

Other Outcome Measures:

1. General Cancer Quality of Life (QoL) Assessment [ Time Frame: 72 weeks ]

   Quality of Life will be assessed via The European Organisation for Research and Treatment of Cancer (EORTC) general cancer specific questionnaire (QLQ-C30).

   For the QLQ-C30 all of the scales and single-item measures range in score from 0 to 100. A high scale score will represent a higher response level. Thus a high score for a functional scale represents a high/healthy level of functioning. A high score for the global health status/QoL represents a high quality of life, but a high score for a symptom scale/item represents a high level of symptomatology/problems.

2. Head and Neck Cancer Quality of Life (QoL) Assessment [ Time Frame: 72 weeks ]

   Quality of Life will also be assessed via The European Organisation for Research and Treatment of Cancer (EORTC) questionnaire designed to assess the quality of life of head and neck cancer patients (QLQ-H&N35).

   For the QLQ-H&N35, all of the scales and single-item measures range in score from 0 to 100. For all the scales and single-items a high score represents a high level of symptomatology or problems.

3. Wound Healing [ Time Frame: 72 weeks ]
   Degree of wound healing at injection site(s) will be assessed using a specifically designed Injection Site Assessment Worksheet, observed at monthly intervals up to 72 weeks
4. Tumour Response Rate Of Both Injected And Non-Injected Tumours [ Time Frame: 72 weeks ]
   Overall Response Rate of both injected and non-injected tumours based on RECIST v1.1.
5. Tumour Response Rate [ Time Frame: 72 weeks ]
   Overall Response Rate based on itRECIST.
6. Evaluation of Peripheral Blood Mononucleocytes (PBMCs) [ Time Frame: 24 weeks ]
   Evaluation of Peripheral Blood Mononucleocytes (PBMCs).
7. Evaluation of circulating tumour DNA (ctDNA) [ Time Frame: 24 weeks ]
   Evaluation of circulating tumour DNA (ctDNA).
8. Tumour Microenvironment [ Time Frame: 14 days after the first treatment. ]
   To assess changes in the tumour microenvironment by looking at the change from baseline of immune cell infiltration in tumour biopsy tissue collected after injection with tigilanol tiglate.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Are willing and able to provide written informed consent for the study prior to any protocol-specific procedures and to comply with all local and study requirements.
2. Are ≥ 18 years of age on the day of providing informed consent.
3. Have a histologically confirmed diagnosis of a solid head and neck malignancy and have either recurrent disease and/or metastatic disease, or have failed on at least one line of systemic therapy. Tumour types can include: HNSCC, sino-nasal cancers, salivary gland cancers, and peri-stomal laryngeal carcinomas with pre-existing tracheostomy.
4. Have disease that is amenable to intratumoural injection either by palpation or under ultrasound guided injection. Lymph nodes with metastatic disease from the patient's head and neck cancer can be selected for treatment. Note: Measurable disease as per RECIST v1.1. is not mandatory.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
6. Have life expectancy of more than 12 weeks.
7. Female participants who are Women of Child-Bearing Potential (WOCBP) must have a negative serum pregnancy test at Screening (within 14 days of the first study drug administration), must be willing to use a highly effective contraception from date of consent, throughout the study period and up to 30 days after the last study drug administration, and must not be breastfeeding.
8. Male participants with a potentially fertile female partner are eligible if they have had a vasectomy or are willing to use adequate contraception from prior to commencement of study drug administration, throughout the study period and up to 30 days after the last study drug administration, and must not donate sperm throughout the study period and up to 30 days after the last study drug administration.

Exclusion Criteria:

1. Are planning to receive intratumoural treatment or radiotherapy to any of the tumours intended for injection within 28 days prior to Screening, or during treatment with tigilanol tiglate.
2. Have a tumour intended for injection that is immediately adjacent to, or with infiltration into, any major artery or vein (e.g., if the tumour for injection is located adjacent to the jugular vein).
3. Have a tumour intended for injection located in an area where post-injection swelling could compromise the airway.
4. Have a tumour intended for injection that is a nasal tumour extending into the Ethmoid sinus.
5. Have had any previous intervention (extensive surgery or radiation therapy) in the area of a tumour intended for injection that is in proximity of the airway (such that tracking of the injected fluid may be unpredictable and could lead to airway swelling). Patients with a permanent tracheostomy can be included.
6. Are receiving or have received other investigational agents or have used an investigational device without undergoing a 28-day (or 5 half-lives, whichever is shorter) wash-out period prior to their first treatment with tigilanol tiglate. These patients must have recovered from all AEs due to previous investigational therapies to ≤ Grade 1 at baseline.
7. Are receiving or have received systemic anticancer therapy, or therapeutic radiation treatment, without undergoing a 28-day (or 5 half-lives, whichever is shorter) wash-out period prior to their first treatment with tigilanol tiglate. These patients must have recovered from all AEs due to previous therapies to ≤ Grade 1 at baseline.
8. Have had major surgery within 28 days of their first treatment with tigilanol tiglate or anticipate the need for major surgery during the study period. Minor surgical procedures are permitted, but with sufficient time for wound healing.
9. Have known, current or history of active cerebral metastasis and/or carcinomatous meningitis.
10. Have any bleeding diathesis or coagulopathy that would make intratumoural injection or biopsy unsafe, or if they are on therapeutic warfarin therapy.
11. Have a history of allergic reactions or severe hypersensitivity (Grade ≥ 3) attributed to tigilanol tiglate or compounds of similar chemical or biologic composition to tigilanol tiglate, any of its excipients or other agents used in the study.
12. In the opinion of the treating Investigator, the patient is not an appropriate candidate for the study for any reason (e.g., they have a known psychiatric or substance abuse disorder that would interfere with their ability to cooperate with the requirements of the study).

Contacts and Locations

Contacts

Contact: Head of Human Clinical Operations; +61 (0) 738 708 933; enquiries@qbiotics.com

Locations

Australia, New South Wales

The Kinghorn Cancer Centre; Recruiting

Sydney, New South Wales, Australia, 2010

Contact: Robert Kent

Principal Investigator: Richard Gallagher, MBBS

United Kingdom

Cardiff and Vale University Health Board - University Hospital of Wales (UHW); Recruiting

Cardiff, United Kingdom, CF14 4XW

Contact: Sara Turley

Principal Investigator: David Owens, MBchB

Guy's Hospital; Not yet recruiting

London, United Kingdom

Contact: Anthony Kong, MBBS

Principal Investigator: Anthony Kong, MBBS

Sponsors and Collaborators

QBiotics Group Limited

Investigators

• Principal Investigator: Richard Gallagher, MBBS; The Kinghorn Cancer Centre
• Principal Investigator: David Owens, MBchB; Cardiff and Vale University Health Board - University Hospital of Wales (UHW)
• Principal Investigator: Anthony Kong, MBBS; Guy's Hospital

More Information

• Responsible Party: QBiotics Group Limited
• ClinicalTrials.gov Identifier: NCT05608876
• Other Study ID Numbers: QB46C-H08; U1111-1282-3152 ( Other Identifier: WHO Universal Trial Number (UTN) )
• First Posted: November 8, 2022
• Last Update Posted: May 31, 2023
• Last Verified: May 2023

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by QBiotics Group Limited:

Squamous cell carcinomas; Sino-nasal cancers; Salivary gland cancers; Peri-stomal laryngeal carcinomas

Additional relevant MeSH terms:

Head and Neck Neoplasms; Neoplasms by Site; Neoplasms