NCT05858710

Study of DPPG2-TSL-DOX Combined With Hyperthermia in Soft Tissue Sarcoma

Phase I Dose Escalation Study of 3-Weekly Intravenous DPPG2-TSL-DOX Combined With Regional Hyperthermia in Locally Advanced or Metastatic Soft Tissue Sarcoma

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (actual)
• Sponsor: Thermosome GmbH · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study aims to explore a new therapeutic approach for advanced soft tissue sarcoma (STS) by investigating the safety, tolerability, and maximum tolerated dose (MTD)/highest tolerated dose (HTD) of DPPG2-TSL-DOX combined with regional hyperthermia (RHT) in patients who have been pre-treated with anthracycline, e.g. doxorubicin (DOX).

Detailed description

Considering that up to 40 percentage of patients with soft tissue sarcoma (STS) will develop metastatic disease and that for these patients overall survival (OS) ranges between 3.7 to 25 months it becomes clear that new therapeutic approaches for the treatment of advanced STS are urgently needed. Doxorubicin (DOX) is a cytotoxic compound that belongs to the class of anthracyclines. DOX has had market authorization since 1960s and is considered the most active chemotherapeutic drug for the treatment of STS. DPPG2-TSL-DOX is a novel formulation of DOX encapsulated in DPPG2-containing thermosensitive liposomes (TSL). Regional hyperthermia (RHT) with a tumor target temperature of ≥41.5 to ≤44 degree of Celsius combined with anthracycline-based chemotherapy has shown to improve survival in patients with localized high-risk STS. Treatment with DPPG2-TSL-DOX aims at combining the confirmed anti-tumor efficacy of anthracyclines in the treatment of locally advanced STS with RHT-triggered DOX release from circulating liposomes resulting in higher local DOX concentrations in the tumor as observed in preclinical studies. DPPG2-TSL-DOX combined with RHT has been investigated in feline sarcoma at 1 mg/kg dose level resembling the clinically recommended dose level of standard DOX with considerably improved efficacy and better tolerability. The proposed study will characterize the safety and tolerability and, if applicable, the maximum tolerated dose (MTD)/highest tolerated dose (HTD) of DPPG2-TSL-DOX in combination with RHT in patients with advanced or metastatic STS who have been pre-treated with anthracycline. An adapted 3+3 MAD study design with sentinel dosing and a starting dose of 20 mg/m\^2 DPPG2-TSL-DOX is applied in this study to identify dose-limiting toxicities (DLTs) of DPPG2-TSL-DOX in combination with RHT.

Conditions

• Sarcoma, Soft Tissue

Interventions

Type	Name	Description
DRUG	DPPG2-TSL-DOX	DPPG2-TSL-DOX is a thermosensitive liposomal formulation of doxorubicin.
DRUG	Dexrazoxane	For cardioprotection of participants.

Timeline

• Start date: 2023-04-19
• Primary completion: 2025-01-30
• Completion: 2025-05-28
• First posted: 2023-05-15
• Last updated: 2025-07-28

Locations

2 sites across 1 country: Germany