Neoadjuvant Irradiation of Extremity Soft Tissue Sarcoma With Ions
Trial Snapshot
- Phase
- Not Applicable
- Status
- Active, not recruiting
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Proportion of therapies without wound healing disorders and/or discontinuation
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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)
Arms & Interventions
Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE))
Arm A: Protons, 39 Gy (RBE) in 13 fractions (single dose 3.0 Gy(RBE))
Intervention: Protons (Radiation)
Arm B: Carbon ions, 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))
Intervention: carbon ions (Radiation)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- 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(from start of radiotherapy to onset of therapy until local and / or distant tumor progression up to 5 years)
- LC: Local control(from start of radiotherapy to local onset to local tumor progression up to 5 years)
- OS: Overall survival(from start of radiotherapy until death or censorship up to 5 years)
Investigators
Juergen Debus
Prof. Dr. Dr.
University Hospital Heidelberg