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Sarcoma,Soft TissuePhase 2TNT-HYPENCT06835049

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

A Phase 2 study testing Doxorubicin, Ifosfamide and Dacarbazine in people with Sarcoma,Soft Tissue, run by Swiss Cancer Institute at 8 sites in Switzerland.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Sarcoma,Soft Tissue
What is being tested?
Doxorubicin, Ifosfamide and Dacarbazine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
8 sitesSwitzerland
Study dates
27 Oct 2025to 31 Mar 2031
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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).

Trial locations and contacts

8 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Gwendoline Wicki contact

+41 31 389 91 91

trials@sakk.ch

8 sites in 1 country

Switzerland8 sites, 8 recruiting

  • Kantonsspital Aarau

    Aarau, 5001

    Oliver Riesterer, Prof., +41 62 838 42 49, oliver.riesterer@ksa.ch

    Oliver Riesterer, Prof.

    Recruiting

  • Universitaetsspital Basel

    Basel, CH-4031

    Fatime Krasniqi, MD, +41 61 265 50 59, fatime.krasniqi@usb.ch

    Fatime Krasniqi, MD

    Recruiting

  • EOC - Istituto Oncologico della Svizzera Italiana

    Bellinzona, 6500

    Thomas Zilli, Prof, +41 91 811 86 75, segretariatoRadioterapia.IOSI@eoc.ch

    Thomas Zilli, Prof

    Recruiting

  • Inselspital Bern - Universitätsklinik für Radioonkologie

    Bern, 3010

    Emanuel Stutz, MD, +41 31 632 26 32, emanuel.stutz@insel.ch

    Emanuel Stutz, MD

    Recruiting

  • CHUV - Swiss Cancer Center Lausanne

    Lausanne, 1011

    Antonia Digklia, MD, +41 21 314 79 28, Antonia.Digklia@chuv.ch

    Antonia Digklia, MD

    Recruiting

  • hoch Health Ostschweiz - Kantonsspital St. Gallen

    Sankt Gallen, 9007

    Christina Appenzeller, MD, +41 71 494 29 22, christina.appenzeller@kssg.ch

    Christina Appenzeller, MD

    Recruiting

  • Kantonsspital Winterthur

    Winterthur, 8401

    Ralph Zachariah, MD, +41 52 266 30 65, ralph.zachariah@ksw.ch

    Ralph Zachariah, MD

    Recruiting

  • Universitätsspital Zürich

    Zurich, 8091

    Lorenz Bankel, MD, +41 44 255 22 14, lorenz.bankel@usz.ch

    Lorenz Bankel, MD

    Recruiting

Other trials in Switzerland

About this study

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

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.

Read the 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.

Being tested
Doxorubicin, Ifosfamide, Dacarbazine, Hyperthermia, Radiotherapy
Keywords
Sarcoma, soft-tissue, TNT-HYPE, phase II, Neoadjuvant Treatment, hyperthermia
Medical subject headings
Sarcoma, Hyperthermia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DoxorubicinDrug

    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.

  • IfosfamideDrug

    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.

  • DacarbazineDrug

    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.

  • HyperthermiaOther

    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.

  • RadiotherapyRadiation

    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.

  • SurgeryProcedure or surgery

    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.

Study groups in NCT06835049
Study groupRoleWhat they receive
Neoadjuvant TreatmentExperimentalTrial 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.
Receives: Drug: Doxorubicin; Drug: Ifosfamide; Drug: Dacarbazine; Other: Hyperthermia; Radiation: Radiotherapy; Procedure: Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Protocol feasibility rate

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

    Measured: End of treatment approx. 20 weeks after registration

Secondary outcomes (1)

  1. Disease-free survival (DFS)

    DFS defined as

    • time from registration until local or distant relapse,
    • or, if tumor has not been operated, time from registration until progression according to RECIST v1.1,
    • or death from any cause, whichever occurs first.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2025
  2. Study start27 Oct 2025
  3. Primary completion31 Mar 2028 (estimated)
  4. Study completion31 Mar 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Multicenter, single arm, open label, phase II trial.
Masking
None (open label)
Enrolment
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06835049
Sponsor's protocol ID
SAKK 57/24
Acronym
TNT-HYPE
Status last verified
Dec 2025
First submitted
13 Feb 2025
Last updated
30 Dec 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Doxorubicin, Ifosfamide and Dacarbazine in people with Sarcoma,Soft Tissue, run by Swiss Cancer Institute at 8 sites in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 30 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Gwendoline Wicki (+41 31 389 91 91, trials@sakk.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Protocol feasibility rate (time frame: End of treatment approx. 20 weeks after registration). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06835049.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Dec 2025.

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