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

NCT05858710 | Completed Phase 1 DMC

• 3 other identifiers: TS-DM-STS-1012023-507836-19-002020-005033-32
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Sarcoma, Soft Tissue

Keywords

Sarcoma, Soft Tissue; Doxorubicin/ IV + Liposomes; Doxorubicin

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  If no more than 1 subject experiencing DLTs is identified after all subjects completed cycle 3 in dose level 3, MTD for the current study and study population will be considered 50 mg/m2.

  End of study (up to 14 months)

• Highest tolerated dose (HTD)

  Highest dose considered safe for dose escalation by the independent DSMB in the FiH study provided \< 33% experiencing a DLT per DL are reported in the study until completion or early termination.

  End of study (up to 14 months)

Secondary Outcomes (22)

• Adverse Events (AEs)

  End of study (up to 14 months)

• Serious Adverse Events (SAEs)

  End of study (up to 14 months)

• Laboratory abnormalities

  End of study (up to 14 months)

• Electrocardiogram (ECG) abnormalities

  End of study (up to 14 months)

• Echocardiogram (ECHO) abnormalities

  End of study (up to 14 months)

Other Outcomes (3)

• Radiographic response

  day 64 (+/-3) in the study for each participant and end of study (21 [+7] days after last study drug treatment)

• Radiographic local response

  day 64 (+/-3) in the study for each participant and end of study (21 [+7] days after last study drug treatment)

• Tumor temperatures (optional)

  day 23, 44, 65, 86, 107 (+/-3) in the study for each participant

Study Arms (1)

IV DPPG2-TSL-DOX

EXPERIMENTAL

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.

Drug: DPPG2-TSL-DOX; Drug: Dexrazoxane

Interventions

DPPG2-TSL-DOX DRUG

DPPG2-TSL-DOX is a thermosensitive liposomal formulation of doxorubicin.

Also known as: Doxorubicin, THE001

IV DPPG2-TSL-DOX

Dexrazoxane DRUG

For cardioprotection of participants.

IV DPPG2-TSL-DOX

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age at the time of consent ≥18 years.
• Patient has provided written informed consent prior to any study-specific procedure.
• Locally advanced (unresectable) or metastatic STS, including histological sarcoma subtypes treated as STS, for which treatment with DOX monotherapy is appropriate, as confirmed by the investigator.
• Pretreatment with an anthracycline (including DOX, epirubicin as mono- or combination therapy). Patients who received anthracycline in an adjuvant setting are eligible.
• Progressive disease not suitable for surgery after
• only one further line of chemotherapy (including TKI) if the RHT field targets the clinically relevant tumor manifestation/s (e.g., locally advanced or multifocal intraabdominal STS; diffuse metastatic STS in which RHT of a tumor manifestation \[e.g., liver\] is considered relevant although other systemic metastases are present that do not endanger the patient, as per the judgment of the investigator), or
• two or more further lines of chemotherapies (including TKI) for patients with metastatic STS and a tumor manifestation suitable for RHT.
• All previous oncological treatments must have been completed ≥3 weeks (21 days) prior to the first dose of study treatment, ensuring a sufficient washout period.
• Measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) (Eisenhauer et al. 2009).
• Tumor accessible for RHT.
• Left ventricular ejection fraction (LVEF) \>50% (within 28 days prior to enrolment).
• Adequate hematologic, organ and coagulation function within 14 days prior to enrolment as assessed by local lab:
• Absolute neutrophil count (ANC) ≥1.5×10\^9/L. Granulocyte-colony stimulating factor (G-CSF) cannot be administered within 2 weeks (14 days) prior to enrolment.
• Platelet count ≥100×10\^9/L.
• Hemoglobin ≥9.0 g/dL. No transfusions are allowed within 2 weeks (14 days) prior to enrolment.

You may not qualify if:

• Patients already enrolled in any clinical study involving an investigational product or medical device or have participated within the past 30 days in a clinical trial involving an investigational product or medical device.
• History of another primary malignancy, with the exception of:
• curatively treated non-melanomatous skin cancer
• curatively treated cervical carcinoma in situ
• non-metastatic prostate cancer, or
• other primary non-hematologic malignancies that had been treated with curative intent, no known active disease, and no treatment administered during the last 3 years prior to enrolment that the investigator agrees will not affect the interpretation of study results or would be unsuitable for participation in the study.
• Active fungal, bacterial and/or known viral infection including human immunodeficiency virus or viral (A, B, or C) hepatitis.
• Uncontrolled intercurrent illness including, but not limited to, an ongoing/active infection requiring parenteral antibiotics.
• Have a serious cardiac condition, such as:
• unstable angina pectoris
• angioplasty, cardiac stenting, or myocardial infarction within 6 months of enrolment
• valvulopathy that is severe, moderate, or deemed clinically significant
• arrhythmias that are symptomatic or require treatment
• Have a QTcF interval of \>450 msec for males and \>470 msec for females on screening electrocardiogram (ECG) utilizing Fridericia's correction.
• Psychiatric illness or social situation that would limit compliance with study requirements.

Sponsors & Collaborators

• Thermosome GmbH: lead

Study Sites (2)

Helios Klinikum Berlin-Buch GmbH

Berlin, 13125, Germany

Location

Klinikum der Universität München (KUM) Campus Großhadern

Munich, 81377, Germany

Location

Related Links

• Sponsor's website giving information on the drug technology

MeSH Terms

Conditions

Sarcoma

Interventions

Doxorubicin; Dexrazoxane

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Razoxane; Diketopiperazines; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Peter Reichardt, PD Dr.

  Helios Klinikum Berlin-Buch GmbH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: an adapted 3+3 multiple ascending dose (MAD) design with sentinel dosing

Study Record Dates

• First Submitted: April 24, 2023
• First Posted: May 15, 2023
• Study Start: April 19, 2023
• Primary Completion: January 30, 2025
• Study Completion: May 28, 2025
• Last Updated: July 28, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)