Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base

Study Overview
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Brief Summary
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This study is a prospective randomised clinical phase III trial. The primary objective of this study is to evaluate, if the innovative therapy (carbon ion irradiation) in chordomas is superior to the standard proton treatment with respect to the local-progression free survival (LPFS).

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 skull base chordomas. 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 chordoma will be randomised to either proton or carbon ion radiation therapy. As a standard, patients will undergo non-invasive, rigid immobilization and target volume delineation will be carried out based on CT and MRI data. The biologically isoeffective target dose to the PTV in carbon ion treatment (accelerated dose) will be 63 Gy E ± 5% and 72 Gy E ± 5% (standard dose) in proton therapy respectively. Local-progression free survival (LPFS) will be analysed as primary end point. Toxicity and survival are the secondary end points. Also matters of interest are patterns of recurrence, prognostic factors and plan quality.

Official Title
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Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-

Conditions
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Chordoma, Tumor, Treatment

Intervention / Treatment
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* Radiation: Carbon ion
* Radiation: Protons


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 chordoma 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 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E. | Radiation: Carbon ion<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 - 63 Gy E ± 5%, further 5-7 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, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 fractions a 2 Gy E. | Radiation: Protons<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, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 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 therapy (carbon ion irradiation) in chordomas is superior to the standard proton treatment with respect to the LPFS defined as time from the randomisation to observed local reccurrence or death from any cause in the absence of documented local disease progression. Lo-cal recurrence defined as MRT or CT - morphological tumor progress in the former irradiated region. A 10% increase in the LPFS is considered clinically relevant as-suming that the LPFS rate for the proton therapy is 70%. | 8-years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | Assessment of overall survival, progression free and metastasis free survival. | 8-years | 
| Local control and patterns of recurrence | Local recurrences will be confirmed radiologically and histologically whenever possible. At least two medical doctors (radiation oncologist and/or radiologist) will be required to judge of the recurrence. | 8 years | 
| Toxicity | Acute and late toxicity will be analysed due to Common Terminology Criteria for Adverse Events: CTCAE V4.0 for acute reaction and RTOG/EORTC for late effects. | 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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base of skull chordoma, radiation, carbon ions, protons