Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE)

Main Inclusion Criteria:

• Histologically confirmed primary high-risk Soft tissue sarcoma (STS) of extremity ortrunk.

• High-risk according to the prognostic Sarculator tool: 10-year OS probability < 60%5.

• Resectable tumor: resectability is based on pre-operative imaging and has to bedefined by the local treating sarcoma team. A patient is not considered resectablewhen the expectation is that only a R2 resection is feasible.

• Measurable disease per RECIST v1.1.

• Diagnostic biopsy is available for the central pathology review.

• Candidate for chemotherapy regimen according to protocol.

• Candidate for loco-regional HT.

• Adequate bone marrow function, hepatic function, renal function, cardiac functionand coagulation function.

Main Exclusion Criteria:

• Metastatic disease.

• Previous Whoops resection.

• Ex-ulcerating tumors or tumors infiltrating the skin.

• Other invasive malignancy within 5 years, with the exception of adequately treatednon melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6prostate cancer.

• Any previous radiotherapy (RT) or systemic therapy for the present tumor.

• Previous treatment with maximum cumulative doses (450 mg/m² doxorubicin orequivalent 900 mg/m² epirubicin) of doxorubicin, daunorubicin, epirubicin,idarubicin, and/or other anthracyclines and anthracenediones.

• Concomitant or recent (within 30 days of registration) treatment with any otherexperimental drug.

• Concomitant use of other anti-cancer drugs or RT.

• No metal implants in the region of tumor or cardiac implant electronic devices (CIEDs).

• Severe or uncontrolled cardiovascular disease (congestive heart failure NYHA III orIV), unstable angina pectoris, history of myocardial infarction within the last 12months, serious arrhythmias requiring medication (with exception of atrialfibrillation or paroxysmal supraventricular tachycardia), significantQT-prolongation, uncontrolled hypertension.

• Active and uncontrolled infections, in particular urinary tract infections.

• Inflammation of the urinary bladder (interstitial cystitis).

• History of cerebrovascular accident or intracranial hemorrhage within 6 months priorto registration.

• Vaccination with live vaccines within 30 days prior to registration.

• Known hypersensitivity to trial drug(s) or to any component of the trial drug(s).