RecruitingPhase 2NCT06835049

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

Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE). A Multicenter, Single Arm, Open Label, Phase II Trial

Sponsor

Swiss Cancer Institute

Enrollment

24 participants

Start Date

Oct 27, 2025

Study Type

INTERVENTIONAL

Conditions

Sarcoma,Soft Tissue

Summary

Soft tissue sarcomas (STSs) are rare cancers with a 5-year survival rate of 60%, and there is no standard treatment for high-risk extremity and trunk STSs (eSTS). A phase III trial suggests that adding moderate regional hyperthermia (HT) to anthracycline-based chemotherapy, followed by surgery and radiotherapy (RT), can improve 10-year overall survival by 10%. This trial aims to optimize treatment by combining the most effective regimens from chemotherapy, HT, RT, and surgery, and will evaluate the feasibility of this new total neoadjuvant treatment (TNT) approach.

Eligibility

Min Age: 18 Years

Inclusion Criteria8

Histologically confirmed primary high-risk Soft tissue sarcoma (STS) of extremity or trunk.
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 be defined by the local treating sarcoma team. A patient is not considered resectable when 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 function and coagulation function.

Exclusion Criteria15

Metastatic disease.
Previous Whoops resection.
Ex-ulcerating tumors or tumors infiltrating the skin.
Other invasive malignancy within 5 years, with the exception of adequately treated non melanoma skin cancer, localized cervical cancer, localized and Gleason ≤ 6 prostate cancer.
Any previous radiotherapy (RT) or systemic therapy for the present tumor.
Previous treatment with maximum cumulative doses (450 mg/m² doxorubicin or equivalent 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 other experimental 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 or IV), unstable angina pectoris, history of myocardial infarction within the last 12 months, serious arrhythmias requiring medication (with exception of atrial fibrillation or paroxysmal supraventricular tachycardia), significant QT-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 prior to 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).

Interventions

DRUGDoxorubicin

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Doxorubicin will be given at a dose of 75 mg/m2 Body surface area (BSA) on day 1 of each cycle as a intravenous infusion over 15 minutes.

DRUGIfosfamide

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Ifosfamide will be given at a dose of 3 g/m2 BSA on days 1 to 3 of each cycle, for a total dose per cycle of 9 g/m2 BSA, as an intravenous infusion of 3 g/m2 daily over 4 hours.

DRUGDacarbazine

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma). Dacarbazine will be given at a daily dose of 300 mg/m2 BSA on days 1 to 3 of each cycle, for a total dose per cycle of 900 mg/m2 BSA, as an intravenous infusion over 30 minutes.

OTHERHyperthermia

Hyperthermia (HT) sessions are scheduled on days 1 and 3 of each chemotherapy cycle. The duration of the preheating phase is always 30 minutes. Together with the treatment phase of 60 minutes, the duration of a HT session is uniformly 90 minutes (Total treatment time). On days 2, chemotherapy will be applied without HT.

RADIATIONRadiotherapy

Radiotherapy (RT) treatment should start ideally 19 days after last chemotherapy dose received (range -4 / +7), preferably on a Monday to omit that the last RT fractions will be applied directly after the weekend. Start of RT can be postponed up to 14 days due to medical reasons without violating treatment protocol. Patients will preferably receive normofractionated RT to a total dose of 50 Gy in 25 fractions of 2 Gy over 5 weeks23. Alternatively, patients can receive a moderate hypofractionated RT to either a total dose of 42.75 Gy in 15 fractions of 2.85 Gy over 3 weeks or a total dose of 42 Gy in 14 fractions of 3 Gy over 2 weeks and four days41. The respective total treatment time changes respectively. The RT treatment should be delivered once daily except on weekends.

PROCEDURESurgery

Standard of care surgical resection must be done by an experienced sarcoma surgeon. All lesions of the trunk and extremities will be resected after total neoadjuvant treatment with chemotherapy, HT and RT. Surgery will take place preferentially 6 weeks (+/- 2 weeks) after end of radiation.