Soft Tissue SarcomaEXTREM IONNCT04946357
Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions
A study testing Protons and carbon ions in people with Soft Tissue Sarcoma, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Soft Tissue Sarcoma
- What is being tested?
- Protons and carbon ions
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteGermany
- Study dates
- 21 Jun 2021to 1 Jul 2029
- Phase
- Interventional
- 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
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital Heidelberg, Department of RadioOncology
Heidelberg, Baden-Wurttemberg, 69120
About this study
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.
Read the 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.
- Conditions
- Soft Tissue Sarcoma
- Being tested
- Protons, carbon ions
- Medical subject headings
- Sarcoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProtonsRadiation
proton irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions
carbon ionsRadiation
carbon ion irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions
| Study group | Role | What they receive |
|---|---|---|
| Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE)) | Experimental | Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE)) Receives: Radiation: Protons |
| Arm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE)) | Experimental | Arm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE)) Receives: Radiation: carbon ions |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of therapies without wound healing disorders and/or discontinuation
Proportion of therapies without wound healing disorders and / or discontinuation in each study arm.
Measured: from the beginning of radiotherapy (day1) until a maximum of 120 days after the resection
Secondary outcomes (4)
LC: Local control
LC: Local control determined from local onset to local tumor progression
Measured: 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
LPFS: locally progression-free survival determined from onset of therapy to local tumor progression
Measured: from start of radiotherapy to onset of therapy of local tumor progression up to 5 years
DFS: Disease-free survival
DFS: Disease-free survival determined from onset of therapy until local and / or distant tumor progression
Measured: from start of radiotherapy to onset of therapy until local and / or distant tumor progression up to 5 years
OS: Overall survival
OS: Overall survival until death or censorship
Measured: from start of radiotherapy until death or censorship up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jun 2021
- Study start21 Jun 2021
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Soft Tissue SarcomaStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juergen Debus, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04946357
- Sponsor's protocol ID
- EXTREM ION
- Acronym
- EXTREM ION
- Status last verified
- Jul 2026
- First submitted
- 21 Jun 2021
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Brugemann D, Lehner B, Kieser M, Krisam J, Hommertgen A, Jaekel C, Harrabi SB, Herfarth K, Mechtesheimer G, Sedlaczek O, Egerer G, Geisbusch A, Uhl M, Debus J, Seidensaal K. Neoadjuvant irradiation of extremity soft tissue sarcoma with ions (Extrem-ion): study protocol for a randomized phase II pilot trial. BMC Cancer. 2022 May 12;22(1):538. doi: 10.1186/s12885-022-09560-x.
PubMed 35550036
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions
- ClinicalTrials.gov ID
- NCT04946357
- Acronym / sponsor ID
- EXTREM ION / EXTREM ION
- Conditions
- Soft Tissue Sarcoma
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- 21 Jun 2021 (actual)
- Primary completion
- 1 Jul 2028 (estimated)
- Study completion
- 1 Jul 2029 (estimated)
- First posted
- 30 Jun 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE)) | Experimental | Radiation: ProtonsArm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE)) |
| Arm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE)) | Experimental | Radiation: carbon ionsArm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE)) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (7 listed)
- Stage IV (distant metastases)
- Lymph node metastasis
- Metal implants that influence treatment planning with ions
- Previous radiotherapy in the treatment area
- Desmoid tumors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protonsproton irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions | Radiation | Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE)) |
| carbon ionscarbon ion irradiation with a total dose of 39 Gy(RBE) in 3 Gy(RBE) fractions | Radiation | Arm B: Carbon ions, 39 Gy(RBE) in 13 fractions (single dose 3.0 Gy(RBE)) |
Primary outcome
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.
4 secondary outcomes
LC: Local control
Time frame: 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
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
OS: Overall survival
Time frame: from start of radiotherapy until death or censorship up to 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Derived from this study: PubMed 35550036Brugemann D, Lehner B, Kieser M, Krisam J, Hommertgen A, Jaekel C, Harrabi SB, Herfarth K, Mechtesheimer G, Sedlaczek O, Egerer G, Geisbusch A, Uhl M, Debus J, Seidensaal K. Neoadjuvant irradiation of extremity soft tissue sarcoma with ions (Extrem-ion): study protocol for a randomized phase II pilot trial. BMC Cancer. 2022 May 12;22(1):538. doi: 10.1186/s12885-022-09560-x.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protons and carbon ions in people with Soft Tissue Sarcoma, run by University Hospital Heidelberg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. 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: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. 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.
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?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). 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 NCT04946357, which also lists 1 linked publication.
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 8 Jul 2026.