Clinical trial NCT06835049: Feasibility of Total Neoadjuvant Treatment With HYPErthermia in Patients With High-risk Extremity and Trunk Soft Tissue Sarcoma (TNT-HYPE)
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Sarcoma,Soft Tissue
Keywords: Sarcoma, soft-tissue
TNT-HYPE
phase II
Neoadjuvant Treatment
hyperthermia
Lead sponsor: Swiss Group for Clinical Cancer Research
Sponsor class: OTHER
First posted: 2025-02-19
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Multicenter, single arm, open label, phase II trial.
Primary purpose: TREATMENT

Brief 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.

Detailed description: Soft tissue sarcomas (STSs) are rare cancers with a 5-year survival rate of only 60%. There is no international standard treatment for high-risk extremity and trunk STSs (eSTS). Current evidence from a phase III trial suggests that adding moderate regional hyperthermia (HT) to anthracycline-based chemotherapy followed by surgery and radiotherapy (RT) can improve survival rates, showing a 10% improvement in 10-year overall survival.

The aim of this trial is to optimize the treatment for this high-risk group. To achieve this, the assumed most effective treatment regimens from each treatment modality (chemotherapy, HT, RT, and surgery) were identified and combined into an optimized treatment protocol. Neoadjuvant chemotherapy in this population is not yet broadly accepted as standard of care. Furthermore, this new total neoadjuvant treatment (TNT) approach has not yet been investigated prospectively and in addition, the patients have to get their HT treatment potentially in a hospital distant from their domicile. Therefore, we will evaluate in this trial the feasibility of this new treatment schedule as primary endpoint.

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma) combined with HT, followed by RT and surgery. Each chemotherapy cycle will last 3 weeks. Trial treatment will last approximately 20 weeks. After surgery, a follow-up period of 36 months per patient is foreseen.

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).

Primary outcomes:
measure: Protocol feasibility rate
timeFrame: End of treatment approx. 20 weeks after registration
Secondary outcomes:
measure: Disease-free survival (DFS)
timeFrame: From the date of registration until the date of local or distant relapse, progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 3 years after registration
Other outcomes:
measure: Objective response rate (ORR)
timeFrame: From the date of registration until the date of progressive disease according to RECIST v1.1 or death, whichever occurs first, assessed up to 3 years after registration
measure: Pathologic complete response (pCR)
timeFrame: End of treatment approx. 20 weeks after registration
Locations:
city: Aarau
country: Switzerland
facility: Kantonsspital Aarau
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Bellinzona
country: Switzerland
facility: EOC - Istituto Oncologico della Svizzera Italiana
city: Bern
country: Switzerland
facility: Inselspital Bern - Universitätsklinik für Radioonkologie
city: Lausanne
country: Switzerland
facility: CHUV - Swiss Cancer Center Lausanne
city: St. Gallen
country: Switzerland
facility: hoch Health Ostschweiz - Kantonsspital St. Gallen
city: Winterthur
country: Switzerland
facility: Kantonsspital Winterthur
city: Zürich
country: Switzerland
facility: Universitätsspital Zürich
Study officials:
affiliation: Insel Gruppe AG, University Hospital Bern
name: Emanuel Stutz, MD
role: STUDY_DIRECTOR
affiliation: University of Bern
name: Attila Kollàr, MD
role: STUDY_CHAIR
References: