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

Phase 3

• Conditions: Chordoma; Tumor; Treatment
• Interventions: Radiation: Carbon ion; Radiation: Protons

• Registration Number: NCT01182779
• Lead Sponsor: Heidelberg University

Brief Summary

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

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.

Study Timeline

• Status Verified: 2010-07
• Study Start: 2010-07
• Study First Submitted: 2010-07-26
• Study First Submitted QC: 2010-08-16
• Last Update Submitted: 2010-08-16
• Study First Posted: 2010-08-17
• Last Update Posted: 2010-08-17
• Primary Completion: 2015-08
• Study Completion: 2023-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 319

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Carbon ion	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.
B	Protons	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.

Primary Outcome Measures

Name	Time	Method
local-progression free survival (LPFS)	8-years	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%.

Secondary Outcome Measures

Name	Time	Method
Survival	8-years	Assessment of overall survival, progression free and metastasis free survival.
Local control and patterns of recurrence	8 years	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.
Toxicity	8 years	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.

Trial Locations

Locations (1)

University of Heidelberg; 🇩🇪 Heidelberg, Germany