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

NCT06835049 | Recruiting Phase 2 DMC

• 1 other identifier: SAKK 57/24
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 8

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.

Conditions

Sarcoma,Soft Tissue

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Protocol feasibility rate

  PFR defined as percentage of patients who are able to finish the following planned trial treatment parts according to protocol

  End of treatment approx. 20 weeks after registration

Secondary Outcomes (1)

• Disease-free survival (DFS)

  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 (2)

• Objective response rate (ORR)

  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

• Pathologic complete response (pCR)

  End of treatment approx. 20 weeks after registration

Study Arms (1)

Neoadjuvant Treatment

EXPERIMENTAL

Trial treatment consists of 3 neoadjuvant cycles of doxorubicin with either ifosfamide or dacarbazine (the latter only in case of leiomyosarcoma) combined with hyperthermia (HT), followed by radiotherapy (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.

Drug: Doxorubicin; Drug: Ifosfamide; Drug: Dacarbazine; Other: Hyperthermia; Radiation: Radiotherapy; Procedure: Surgery

Interventions

Doxorubicin DRUG

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.

Neoadjuvant Treatment

Ifosfamide DRUG

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.

Neoadjuvant Treatment

Dacarbazine DRUG

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.

Neoadjuvant Treatment

Hyperthermia OTHER

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.

Neoadjuvant Treatment

Radiotherapy RADIATION

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.

Neoadjuvant Treatment

Surgery PROCEDURE

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.

Neoadjuvant Treatment

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Swiss Cancer Institute: lead

Study Sites (8)

Kantonsspital Aarau

Aarau, 5001, Switzerland

RECRUITING

Universitaetsspital Basel

Basel, CH-4031, Switzerland

RECRUITING

EOC - Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

RECRUITING

Inselspital Bern - Universitätsklinik für Radioonkologie

Bern, 3010, Switzerland

RECRUITING

CHUV - Swiss Cancer Center Lausanne

Lausanne, 1011, Switzerland

RECRUITING

hoch Health Ostschweiz - Kantonsspital St. Gallen

Sankt Gallen, 9007, Switzerland

RECRUITING

Kantonsspital Winterthur

Winterthur, 8401, Switzerland

RECRUITING

Universitätsspital Zürich

Zurich, 8091, Switzerland

RECRUITING

MeSH Terms

Conditions

Sarcoma; Hyperthermia

Interventions

Doxorubicin; Ifosfamide; Dacarbazine; Diathermy; Radiotherapy; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Body Temperature Changes; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Heat Stress Disorders; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Triazenes; Imidazoles; Azoles; Hyperthermia, Induced; Therapeutics

Study Officials

• Emanuel Stutz, MD

  Insel Gruppe AG, University Hospital Bern

  STUDY DIRECTOR

• Attila Kollàr, MD

  University of Bern

  STUDY CHAIR

Central Study Contacts

Gwendoline Wicki

CONTACT

+41 31 389 91 91; trials@sakk.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, single arm, open label, phase II trial.

Study Record Dates

• First Submitted: February 13, 2025
• First Posted: February 19, 2025
• Study Start: October 27, 2025
• Primary Completion (Estimated): March 31, 2028
• Study Completion (Estimated): March 31, 2031
• Last Updated: December 30, 2025

Record last verified: 2025-12

Locations

CH (8)