Study of DPPG2-TSL-DOX Combined with Hyperthermia in Soft Tissue Sarcoma
- Conditions
- Sarcoma, Soft Tissue
- Interventions
- Drug: DPPG2-TSL-DOX
- Registration Number
- NCT05858710
- Lead Sponsor
- Thermosome GmbH
- Brief Summary
This study aims to explore a new therapeutic approach for advanced soft tissue sarcoma (STS) by investigating the safety, tolerability, and maximum tolerable dose (MTD) 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 tolerable dose (MTD) 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 9
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description IV DPPG2-TSL-DOX DPPG2-TSL-DOX DPPG2-TSL-DOX (20 or 40 or 50 mg/m\^2) + regional hyperthermia (RHT) 3 dose levels are planned in this study: dose level 1 will be receiving 20 mg/m\^2 DPPG2-TSL-DOX, dose level 2 will be receiving 40 mg/m\^2 DPPG2-TSL-DOX, dose level 3 will be receiving 50 mg/m\^2 DPPG2-TSL-DOX. Participants are to be treated with DPPG2-TSL-DOX infusion over 30 minutes and RHT every three weeks (one cycle = 21 days), receiving up to 6 cycles in Main Study Phase and additional 6 cycles in Treatment Continuation Phase, if eligible: * In the first cycle (cycle 1), DPPG2-TSL-DOX application will be performed without RHT in all participants for safety precaution. * In cycles 2-12, DPPG2-TSL-DOX will be applied in parallel with RHT. Dexrazoxane as cardioprotectant will be provided for participants overcoming a cumulative dose of 300 mg/m\^2 DOX. IV DPPG2-TSL-DOX Dexrazoxane DPPG2-TSL-DOX (20 or 40 or 50 mg/m\^2) + regional hyperthermia (RHT) 3 dose levels are planned in this study: dose level 1 will be receiving 20 mg/m\^2 DPPG2-TSL-DOX, dose level 2 will be receiving 40 mg/m\^2 DPPG2-TSL-DOX, dose level 3 will be receiving 50 mg/m\^2 DPPG2-TSL-DOX. Participants are to be treated with DPPG2-TSL-DOX infusion over 30 minutes and RHT every three weeks (one cycle = 21 days), receiving up to 6 cycles in Main Study Phase and additional 6 cycles in Treatment Continuation Phase, if eligible: * In the first cycle (cycle 1), DPPG2-TSL-DOX application will be performed without RHT in all participants for safety precaution. * In cycles 2-12, DPPG2-TSL-DOX will be applied in parallel with RHT. Dexrazoxane as cardioprotectant will be provided for participants overcoming a cumulative dose of 300 mg/m\^2 DOX.
- Primary Outcome Measures
Name Time Method Maximum tolerated dose (MTD) End of study (up to 14 months) Assessment of the maximum tolerated dose based on the adapted 3+3 method
- Secondary Outcome Measures
Name Time Method Adverse Events (AEs) End of study (up to 14 months) Number of treatment-emergent AEs according to CTCAE 5.0
Serious Adverse Events (SAEs) End of study (up to 14 months) Number of treatment-emergent SAEs according to CTCAE 5.0
Laboratory abnormalities End of study (up to 14 months) Number of laboratory abnormalities
Electrocardiogram (ECG) abnormalities End of study (up to 14 months) Number of participants with ECG abnormalities
Echocardiogram (ECHO) abnormalities End of study (up to 14 months) Number of participants with ECHO abnormalities
Renal toxicities End of study (up to 14 months) Number of participants with renal toxicities
Maximum concentration (Cmax) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) without RHT (cycle 1; 12 time points)
Last measurable (non-zero) concentration (Clast) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Area under the curve from time 0 to x hours (AUC[0-x] ) after the start of infusion of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Area under the curve from time 0 to the time of the last quantifiable concentration (AUC[0-tlast) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Time of maximum observed concentration (Tmax) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Terminal half-life (T½) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Clearance (CL) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Volume of distribution at steady-state (Vss) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Maximum concentration obtained after administration (Cmax) of DPPG2, non-liposomal DOX, liposomal encapsulated DOX and total DOX End of study (upto 14 months) with RHT (cycle 2; 12 time points)
Trial Locations
- Locations (2)
Helios Klinikum Berlin-Buch GmbH
🇩🇪Berlin, Germany
Klinikum der Universität München (KUM) Campus Großhadern
🇩🇪Munich, Germany