Clinical trial NCT01182753: Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Chondrosarcoma
Keywords: Chondrosarcoma
Radiation
carbon ion
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2010-08-17
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Local-Progression Free Survival (LPFS)
timeFrame: 5 years
Secondary outcomes:
measure: Survival
timeFrame: 12 years
measure: Toxicity
timeFrame: 12 years
measure: Patterns of recurrence and local control rate
timeFrame: 5 years
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University of Heidelberg
state: Im neuenheimer Feld 400
Study officials:
affiliation: Heidelberg University
name: Juergen Debus, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schulz-Ertner D, Nikoghosyan A, Hof H, Didinger B, Combs SE, Jakel O, Karger CP, Edler L, Debus J. Carbon ion radiotherapy of skull base chondrosarcomas. Int J Radiat Oncol Biol Phys. 2007 Jan 1;67(1):171-7. doi: 10.1016/j.ijrobp.2006.08.027. Epub 2006 Oct 23.
citation: Munzenrider JE, Liebsch NJ. Proton therapy for tumors of the skull base. Strahlenther Onkol. 1999 Jun;175 Suppl 2:57-63. doi: 10.1007/BF03038890.
citation: Ares C, Hug EB, Lomax AJ, Bolsi A, Timmermann B, Rutz HP, Schuller JC, Pedroni E, Goitein G. Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report. Int J Radiat Oncol Biol Phys. 2009 Nov 15;75(4):1111-8. doi: 10.1016/j.ijrobp.2008.12.055. Epub 2009 Apr 20.
citation: Hug EB, Slater JD. Proton radiation therapy for chordomas and chondrosarcomas of the skull base. Neurosurg Clin N Am. 2000 Oct;11(4):627-38.
citation: Hug EB, Loredo LN, Slater JD, DeVries A, Grove RI, Schaefer RA, Rosenberg AE, Slater JM. Proton radiation therapy for chordomas and chondrosarcomas of the skull base. J Neurosurg. 1999 Sep;91(3):432-9. doi: 10.3171/jns.1999.91.3.0432.
citation: Weber DC, Rutz HP, Pedroni ES, Bolsi A, Timmermann B, Verwey J, Lomax AJ, Goitein G. Results of spot-scanning proton radiation therapy for chordoma and chondrosarcoma of the skull base: the Paul Scherrer Institut experience. Int J Radiat Oncol Biol Phys. 2005 Oct 1;63(2):401-9. doi: 10.1016/j.ijrobp.2005.02.023.
citation: Nikoghosyan AV, Rauch G, Munter MW, Jensen AD, Combs SE, Kieser M, Debus J. Randomised trial of proton vs. carbon ion radiation therapy in patients with low and intermediate grade chondrosarcoma of the skull base, clinical phase III study. BMC Cancer. 2010 Nov 5;10:606. doi: 10.1186/1471-2407-10-606.