Total pre-surgery chemotherapy plus regional hyperthermia for high-risk limb 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

This trial will test whether giving three cycles of chemotherapy with regional hyperthermia before radiation and surgery is feasible and tolerable for people with high-risk soft tissue sarcoma of the arms, legs, or trunk.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Swiss Cancer Institute (Academic / other)
• Drugs / interventions: chemotherapy, doxorubicin
• Locations: 8 sites (Aarau and 7 other locations)
• Trial ID: NCT06835049 on ClinicalTrials.gov

What this trial studies

This phase II trial combines three neoadjuvant cycles of doxorubicin with either ifosfamide (or dacarbazine for leiomyosarcoma) together with regional moderate hyperthermia, followed by radiotherapy and surgery. Each chemotherapy cycle lasts three weeks and the full neoadjuvant program takes about 20 weeks, with surgical resection afterward and 36 months of follow-up. The primary goal is to test feasibility of delivering this total neoadjuvant treatment (TNT), including the practicalities of providing hyperthermia which may require travel to specialized centers. The protocol targets patients with resectable, measurable high-risk extremity or trunk soft tissue sarcoma and requires adequate organ function and no metastatic disease.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed, resectable high-risk extremity or trunk soft tissue sarcoma (per Sarculator risk <60% 10‑year OS), measurable disease by RECIST, no metastases, and adequate organ and cardiac function who are candidates for anthracycline-based chemotherapy and regional hyperthermia.

Not a fit: Patients with metastatic or unresectable disease, tumors infiltrating or ulcerating the skin, prior whoops resection, recent other invasive cancers, or inadequate organ function are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If feasible and safe, this combined preoperative approach could improve long-term survival and local control compared with historical approaches and may increase chances of limb preservation.

How similar studies have performed: A prior phase III trial showed that adding regional hyperthermia to anthracycline-based chemotherapy improved 10-year overall survival by about 10%, but the specific total neoadjuvant combination in this trial has not been prospectively tested.

Eligibility criteria

Main Inclusion Criteria:

* 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.

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 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).

Where this trial is running

Aarau and 7 other locations

• Kantonsspital Aarau — Aarau, Switzerland (Recruiting)
• Universitaetsspital Basel — Basel, Switzerland (Recruiting)
• EOC - Istituto Oncologico della Svizzera Italiana — Bellinzona, Switzerland (Recruiting)
• Inselspital Bern - Universitätsklinik für Radioonkologie — Bern, Switzerland (Recruiting)
• CHUV - Swiss Cancer Center Lausanne — Lausanne, Switzerland (Recruiting)
• hoch Health Ostschweiz - Kantonsspital St. Gallen — Sankt Gallen, Switzerland (Recruiting)
• Kantonsspital Winterthur — Winterthur, Switzerland (Recruiting)
• Universitätsspital Zürich — Zurich, Switzerland (Recruiting)

Study contacts

• Study coordinator: Gwendoline Wicki

Conditions Sarcoma,Soft Tissue; Sarcoma, soft-tissue; TNT-HYPE; phase II; Neoadjuvant Treatment; hyperthermia