Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base

Study Overview
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Brief Summary
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The study is a prospective randomised clinical phase III trial. Proton therapy is the gold standard in the treatment of low and intermediate grad chondrosarcomas of the skull base. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors. Up until now it was impossible to compare two different particle therapies, i.e. proton and carbon ion therapy directly with each other. The aim of this study is to find out, whether the biological advantages of carbon ion therapy mentioned above can also be clinically confirmed.

Detailed Description
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The study is a prospective randomised clinical phase III trial. The trial will be carried out at Heidelberger Ionenstrahl-Therapie (HIT) centre as monocentric trial. Proton therapy is the gold standard in the treatment of low and intermediate grad chondrosarcomas of the skull base. However, high-LET beams such as carbon ions theoretically offer biologic advantages by enhanced biologic effectiveness in slow-growing tumors. Up until now it was impossible to compare two different particle therapies, i.e. proton and carbon ion therapy directly with each other. The aim of this study is to find out, whether the biological advantages of carbon ion therapy mentioned above can also be clinically confirmed. Patients with skull base chondrosarcomas will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume definition will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment will be 60 Gy E ± 5% and 70 Gy E ± 5% (standard dose) in proton therapy respectively. The 5 year local-progression free survival (LPFS) rate will be analysed as primary end point. Overall survival, progression free and metastasis free survival, patterns of recurrence, local control rate and morbidity are the secondary end points. Plan quality is also a matter of interest.

Official Title
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Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base, Clinical Phase III Study

Conditions
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Chondrosarcoma

Intervention / Treatment
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* Radiation: carbon ion therapy
* Radiation: proton therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Karnofsky Performance Score ≥60% Age >18 years and <80 years Informed consent signed by the patient Histological confirmation of low/ intermediate grade chondrosarcoma with infiltration of the skull base. Exclusion Criteria: Inability to understand the aims of the study, no informed consent Prior RT of skull base region Other malignancies with disease-free interval < 5 years (excepting pre-cancerous lesions) Participation in another trial Pregnancy Simultaneous CHT or Immunotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Arm A (carbon ion therapy): Total dose to the PTV2 - 45 Gy E in 3 Gy E /d, 4 - 6 days a week, 15 fractions Total dose to the PTV1 - 60 Gy E ± 5%, further 4 - 6 fractions a 3 Gy E. | Radiation: carbon ion therapy<br>* Arm A (carbon ion therapy): Total dose to the PTV2 - 45 Gy E in 3 Gy E /d, 4 - 6 days a week, 15 fractions Total dose to the PTV1 - 60 Gy E ± 5%, further 4 - 6 fractions a 3 Gy E.<br>|
| Active Comparator: B<br>Arm B (proton therapy): Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E /d, 4 - 6 days a week, 25 - 28 fractions Total dose to the PTV1 - 70 Gy E ± 5%, further 6 - 10 fractions a 2 Gy E. | Radiation: proton therapy<br>* Arm B (proton therapy): Total dose to the PTV2 - 50 to 56 Gy E in 2 Gy E /d, 4 - 6 days a week, 25 - 28 fractions Total dose to the PTV1 - 70 Gy E ± 5%, further 6 - 10 fractions a 2 Gy E.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local-Progression Free Survival (LPFS) | The primary objective of this study is to evaluate, if the innovative carbon ion therapy in chondrosarcomas is not relevantly inferior to the standard proton treatment with respect to the 5 year LPFS rate defined as time from the randomisation to observed local reccurrence. It is assumed that the LPFS rate for the proton therapy is 90%. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Assessment of overall survival, progression free and metastasis free survival. | 12 years | 
| Toxicity | Acute and late toxicity will be analysed according to Common Terminology Criteria for Adverse Events: CTCAE V4.0 for acute side effects and RTOG/EORTC for late reaction. | 12 years | 
| Patterns of recurrence and local control rate | Local recurrences will be confirmed radiologically and histologically whenever possi-ble. At least two medical doctors (radiation oncologist and/or radiologist) will be re-quired to judge of the recurrence. | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chondrosarcoma, Radiation, carbon ion