Clinical trial NCT04946357: Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions
Official title: Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Soft Tissue Sarcoma
Lead sponsor: University Hospital Heidelberg
Sponsor class: OTHER
First posted: 2021-06-30
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Proportion of therapies without wound healing disorders and/or discontinuation
timeFrame: from the beginning of radiotherapy (day1) until a maximum of 120 days after the resection
Secondary outcomes:
measure: LC: Local control
timeFrame: from start of radiotherapy to local onset to local tumor progression up to 5 years
measure: LPFS: locally progression-free survival determined from onset of therapy to local tumor progression
timeFrame: from start of radiotherapy to onset of therapy of local tumor progression up to 5 years
measure: DFS: Disease-free survival
timeFrame: from start of radiotherapy to onset of therapy until local and / or distant tumor progression up to 5 years
measure: OS: Overall survival
timeFrame: from start of radiotherapy until death or censorship up to 5 years
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University Hospital Heidelberg, Department of RadioOncology
state: Baden-Württemberg
Study officials:
References:
citation: 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.