Clinical trial NCT05755113: A Clinical Study to Investigate the Efficacy of Intratumoral Tigilanol Tiglate in Soft Tissue Sarcoma
Official title: A Phase IIa Open Label Study Evaluating the Preliminary Efficacy of Intratumoural Tigilanol Tiglate in Advanced and/or Metastatic Soft Tissue Sarcoma of the Extremities and Body Wall.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Soft Tissue Sarcoma
Keywords: extremeties
body wall
advanced
metastatic
Lead sponsor: QBiotics Group Limited
Sponsor class: INDUSTRY
First posted: 2023-03-06
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open label, single arm. Stage 1 - 10 evaluable participants, max of 5 treatments, 28 days apart. Stage 2 - up to 40 evaluable participants with a maximum of 10 participants in each of four histologically different groups: (i) angiosarcoma, (ii) leiomyosarcoma, (iii) myxofibrosarcoma, and (iv) other mixed origin sarcomas, max of 3 treatments, 7 days apart.
Primary purpose: TREATMENT

Brief summary: A Phase IIa open label study evaluating the preliminary efficacy of intratumoural tigilanol tiglate in advanced and/or metastatic soft tissue sarcoma of the extremities and body wall.

Detailed description: Primary Objective

1. To evaluate tumour ablation in tumours and/or tumour segments following one or more treatments with tigilanol tiglate; and
2. To evaluate the effect of tigilanol tiglate on overall disease control (not limited to injected tumours) (Stage 2 only).

Secondary Objective

1. To assess the safety and tolerability of intratumoural injections with tigilanol tiglate; and
2. To evaluate systemic exposure through pharmacokinetic (PK) assessment after a single intratumoural injection of tigilanol tiglate.

Exploratory Objectives

1. To evaluate the microenvironment of injected tumours +/- non-injected tumours;
2. To evaluate the degree of immune response elicited with intratumoural tigilanol tiglate;
3. To evaluate local recurrence rate; and
4. To evaluate metabolites after a single intratumoural injection of tigilanol tiglate (Stage 2 only).

Eligibility 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 advanced and/or metastatic disease of the body wall or extremities that is amenable to intratumoural injection either by palpation or under ultrasound guided injection, that has been histologically or pathologically confirmed as an STS. STS located on the scalp may also be considered for treatment.
4. Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
5. Have life expectancy of more than 12 weeks.
6. Have adequate renal and hepatic function as assessed by the Investigator.
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. 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.
4. Are receiving or have received systemic anticancer therapy, 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. Patients with ≤ Grade 2 neuropathy may be eligible following discussion with Sponsor Medical Monitor.
5. 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.
6. Have known, active brain metastases and/or carcinomatous meningitis. Participants who have previously treated brain metastases and are neurologically stable can be included.
7. Have any bleeding diathesis or coagulopathy that would make intratumoural injection or biopsy unsafe, or if they are on therapeutic warfarin therapy.
8. 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.
9. In the opinion of the treating Investigator, they are not an appropriate candidate for the study for any reason (e.g., they have known psychiatric or substance abuse disorder that would interfere with their ability to cooperate with the requirements of the study.

Primary outcomes:
measure: Tumour Response
timeFrame: 6 months
measure: ORR as determined by RECIST
timeFrame: 3 and 6 months post initial treatment (Stage 2 only)
Secondary outcomes:
measure: Incidence of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: 6 months
measure: Systemic Exposure
timeFrame: Up to 24 hours after the first dose
Other outcomes:
measure: Tumour Microenvironment
timeFrame: 7 days before and between 28 and 56 days after standard of care (Stage 2).
measure: Evaluation of Peripheral Blood Mononucleocytes (PBMCs)
timeFrame: 24 weeks
measure: Local Recurrence Rate at injection site(s)
timeFrame: 6 months
measure: Metabolite analysis
timeFrame: 24hrs following first injection.
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Centre
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Edmund Bartlett, MD
role: PRINCIPAL_INVESTIGATOR
References: