Intratumoral Tigilanol Tiglate for Soft Tissue Sarcoma

Overseen By Head of Human Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: QBiotics Group Limited

Must not be taking: Warfarin

Disqualifiers: Brain metastases, Major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 6 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires a 28-day period without taking any systemic anticancer therapy or investigational agents before starting the study treatment. This means you may need to stop certain medications, but it's best to discuss your specific situation with the study team.

What makes the drug Tigilanol Tiglate unique for treating soft tissue sarcoma?

Tigilanol Tiglate is unique because it is administered directly into the tumor (intratumoral), which is different from many other treatments that are given systemically (throughout the body). This localized approach may help target the tumor more precisely and reduce side effects. ^{1 2 3 4 5}

Research Team

Edmund Bartlett, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with advanced soft tissue sarcoma in limbs or body wall, able to consent and follow study rules. They must have a life expectancy over 12 weeks, be relatively active (ECOG ≤ 2), and not pregnant or breastfeeding. Participants need functioning kidneys and liver, agree to use contraception, and can't have major blood vessel tumors or recent treatments that conflict with the trial.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

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

I am 18 years old or older.

Exclusion Criteria

I plan to have direct tumor treatment or radiation within 28 days before screening or while on tigilanol tiglate.

My tumor is near or has spread into a major blood vessel.

I haven't had major surgery in the last 28 days and don't expect to need any during the study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive single or multiple intratumoural injections of tigilanol tiglate at up to a fixed dose of 3.6 mg/m2

6 months

Multiple visits for injections and assessments

Follow-up

Participants are monitored for safety, efficacy, and local recurrence rate after treatment

6 months

Regular follow-up visits for monitoring

Pharmacokinetic Assessment

Evaluation of systemic exposure and metabolite analysis after a single intratumoural injection

24 hours

1 visit for blood sampling

Treatment Details

Interventions

• Tigilanol Tiglate

Trial Overview The trial is testing Tigilanol Tiglate's effectiveness when injected directly into tumors of patients with advanced soft tissue sarcomas. It's an open-label Phase IIa study meaning everyone gets the treatment and both doctors and participants know what's being given.

Participant Groups

Group I: Single Arm, Open Label Experimental Treatment 1 Intervention

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.

Tigilanol Tiglate is already approved in European Union, United States for the following indications:

Approved in European Union as Stelfonta for:

• Non-resectable, non-metastatic subcutaneous mast cell tumors located at or distal to the elbow or the hock, and non-resectable, non-metastatic cutaneous mast cell tumors in dogs

Approved in United States as Stelfonta for:

• Non-metastatic, skin-based (cutaneous) mast cell tumors (MCTs) and non-metastatic MCTs located under the dog's skin (subcutaneous), in particular areas of a dog's leg

Who Is Running the Clinical Trial?

QBiotics Group Limited

Lead Sponsor

Trials

4

Recruited

80+

Findings from Research

Ecteinascidin-743 (ET-743) demonstrated antitumoral activity in advanced soft tissue sarcoma patients, with a 4% overall response rate and a 24% disease progression control rate at 6 months, indicating some effectiveness in a challenging patient population.

The treatment had a manageable safety profile, although 50% of patients experienced significant liver enzyme elevations and 61% had severe neutropenia, with two treatment-related deaths occurring due to complications likely linked to protocol violations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. Yovine, A., Riofrio, M., Blay, JY., et al.[2018]

In a study of 11 patients with sarcoma, nanosomal docetaxel lipid suspension (NDLS) chemotherapy showed promising efficacy, with a 50% overall response rate and a 66.7% disease control rate in metastatic cases, indicating its potential effectiveness in treating this type of cancer.

NDLS-based chemotherapy was well tolerated, with no new safety concerns identified, although 63.6% of patients experienced at least one adverse event, primarily hematological and gastrointestinal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study. Narayanan, P., Dattatreya, PS., Prasanna, R., et al.[2022]

The designer peptide [D]-K3H3L9 showed significant cytotoxic and antiproliferative effects against soft tissue sarcoma cell lines in vitro, indicating its potential as an effective treatment option.

In vivo studies in athymic and syngeneic mouse models demonstrated that intratumoral administration of [D]-K3H3L9 significantly inhibited tumor progression and exhibited antiangiogenic properties, suggesting a promising therapeutic mechanism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of soft tissue sarcoma growth by a host defense-like lytic peptide. Steinstraesser, L., Hauk, J., Schubert, C., et al.[2021]

In a study involving 36 patients with advanced soft tissue sarcoma, edatrexate showed a partial response rate of 14%, with notable effectiveness in patients with malignant fibrous histiocytoma (MFH), where 5 out of 7 patients experienced a partial response.

While the overall activity of edatrexate was limited, it was generally well-tolerated, with mild myelosuppression and manageable side effects like fatigue and rash, suggesting that further research is needed, particularly for MFH patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edatrexate in patients with soft tissue sarcoma. Activity in malignant fibrous histiocytoma. Casper, ES., Christman, KL., Schwartz, GK., et al.[2019]

Ecteinascidin (ET-743) demonstrated promising antitumor activity in patients with advanced soft tissue sarcoma, achieving an 8% partial response rate and a 56% progression arrest rate in specific sarcoma types, indicating its potential effectiveness as a second- or third-line treatment.

The treatment was associated with manageable safety concerns, primarily reversible liver enzyme elevations and neutropenia, with no cumulative toxicities observed, and a median overall survival of 9.2 months in heavily pretreated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. Le Cesne, A., Blay, JY., Judson, I., et al.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Phase II study of ecteinascidin-743 in advanced pretreated soft tissue sarcoma patients. [2018]

2. Egypt pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Suppression of soft tissue sarcoma growth by a host defense-like lytic peptide. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Edatrexate in patients with soft tissue sarcoma. Activity in malignant fibrous histiocytoma. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Phase II study of ET-743 in advanced soft tissue sarcomas: a European Organisation for the Research and Treatment of Cancer (EORTC) soft tissue and bone sarcoma group trial. [2018]