Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base (HIT-1)

Heidelberg University

Status and phase: Unknown; Phase 3

Conditions: Treatment; Chordoma; Tumor

Treatments: Radiation: Carbon ion; Radiation: Protons

Study type: Interventional

Funder types: Other

Identifiers

NCT01182779

HIT-1

Details and patient eligibility

About

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).

Full 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.

Enrollment: 319 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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319 participants in 2 patient groups

A

Experimental group

Description:

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.

Treatment:

Radiation: Carbon ion

B

Active Comparator group

Description:

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.

Treatment:

Radiation: Protons