Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions (EXTREM ION)

March 31, 2026 updated by: Juergen Debus, University Hospital Heidelberg
This randomized prospective open-label phase 2 trial testes the safety and feasibility of a hypofractionated accelerated neoadjuvant proton or carbon ion radiotherapy based on the rate of wound healing disorders from beginning of radiotherapy to maximum 120 days after the planned tumor resection or discontinuation of treatment due to any reason. The treatment is of shorter duration (2-3 weeks vs. 5 weeks standard treatment), which should please most patients and thus enhance quality of life. The treatment regimen furthermore promises a reduced rate of late side effects and significant optimization of the current treatment standards. A phase II trial is mandatory not only for obtaining the safety and feasibility data, but also in order to prepare a concurrent phase III trial. Due to the low incidence of soft tissue sarcoma, only a well prepared multicenter study has a chance to be successfully completed based on previous experiences in trials for seldom tumor entities.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Oncologic complete local excision (wide resection) combined with radiotherapy forms the standard treatment for patients with soft tissue sarcoma. Especially patients with G2/G3 sarcomas profit from the combination of radiotherapy and surgery. Well-differentiated sarcomas (G1) after total resection (R0) receive no subsequent treatment besides surgery. The sequence of surgery and radiation therapy is widely discussed by the radiation oncologists and surgeons. The main advantages of neoadjuvant (pre-operative) radiotherapy are the smaller treatment target volumes and reduced prescribed radiation doses of 50 Gy vs. 66 Gy (postoperative) in 2 Gy single doses. Thus, due to these reductions in volumes and dose, neoadjuvant radiotherapy is associated with a lower rate of radiotherapy-associated edema and fibrosis. However, a randomized phase III study showed an increased rate of wound healing complications in patients with neoadjuvant radiotherapy compared to adjuvant (post-operative) radiotherapy (35% vs. 17%). For this reason, adjuvant radiotherapy in is currently preferred in cases with good operability.

Particle therapy bears the chance to utilize the advantages of preoperative radiotherapy without compromising wound healing. The advantages of tumor treatment by ion therapy are based on their special biological and physical features. Protons and carbons ion lead to an improved dose distribution compared to photons which allows an improved sparing of the neighboring risk organs and at the same time an escalation of the dose prescribed to the tumor. Carbon ions are furthermore superior to protons by biological advantages based on their enhanced biological effectivity. In general, heavy ions are considered as a good treatment option for tumors of low radiosensitivity as sarcomas. Superior survival and decreased toxicity rates are expected from the use of protons and carbon ions.

This randomized prospective open-label phase 2 trial testes the safety and feasibility of a hypofractionated accelerated neoadjuvant proton or carbon ion radiotherapy based on the rate of wound healing disorders from beginning of radiotherapy to maximum 120 days after the planned tumor resection or discontinuation of treatment due to any reason. The treatment is of shorter duration (2-3 weeks vs. 5 weeks standard treatment), which should please most patients and thus enhance quality of life. The treatment regimen furthermore promises a reduced rate of late side effects and significant optimization of the current treatment standards. A phase II trial is mandatory not only for obtaining the safety and feasibility data, but also in order to prepare a concurrent phase III trial. Due to the low incidence of soft tissue sarcoma, only a well prepared multicenter study has a chance to be successfully completed based on previous experiences in trials for seldom tumor entities.

Study Type

Interventional

Enrollment (Estimated)

42

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Histologically confirmed soft-tissue sarcoma of the extremities with an indication for perioperative radiation treatment
  • Resectable or marginally resectable
  • Karnofsky index of ≥ 70%
  • Age ≥ 18 years
  • Carried out patient education and written consent
  • Patient is capable to give informed consent

Exclusion Criteria:

  • Stage IV (distant metastases)
  • Lymph node metastasis
  • Metal implants that influence treatment planning with ions
  • Previous radiotherapy in the treatment area
  • Desmoid tumors
  • Simultaneous participation in another clinical trial that could influence the results of the study.
  • Active medical implants for which no ion beam irradiation permit exists at the time of treatment (e.g., cardiac pacemaker, defibrillator)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE))
Radiation: Protons
proton irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions
Experimental: Arm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE))
Radiation: carbon ions
carbon ion irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of therapies without wound healing disorders and/or discontinuation
Time Frame: from the beginning of radiotherapy (day1) until a maximum of 120 days after the resection
Proportion of therapies without wound healing disorders and / or discontinuation in each study arm.
from the beginning of radiotherapy (day1) until a maximum of 120 days after the resection

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LC: Local control
Time Frame: from start of radiotherapy to local onset to local tumor progression up to 5 years
LC: Local control determined from local onset to local tumor progression
from start of radiotherapy to local onset to local tumor progression up to 5 years
LPFS: locally progression-free survival determined from onset of therapy to local tumor progression
Time Frame: from start of radiotherapy to onset of therapy of local tumor progression up to 5 years
LPFS: locally progression-free survival determined from onset of therapy to local tumor progression
from start of radiotherapy to onset of therapy of local tumor progression up to 5 years
DFS: Disease-free survival
Time Frame: from start of radiotherapy to onset of therapy until local and / or distant tumor progression up to 5 years
DFS: Disease-free survival determined from onset of therapy until local and / or distant tumor progression
from start of radiotherapy to onset of therapy until local and / or distant tumor progression up to 5 years
OS: Overall survival
Time Frame: from start of radiotherapy until death or censorship up to 5 years
OS: Overall survival until death or censorship
from start of radiotherapy until death or censorship up to 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital Heidelberg

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 21, 2021

Primary Completion (Estimated)

July 1, 2028

Study Completion (Estimated)

July 1, 2029

Study Registration Dates

First Submitted

June 21, 2021

First Submitted That Met QC Criteria

June 29, 2021

First Posted (Actual)

June 30, 2021

Study Record Updates

Last Update Posted (Actual)

April 6, 2026

Last Update Submitted That Met QC Criteria

March 31, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EXTREM ION

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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