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

Chondrosarcoma Clinical Trial

— CSP12C  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01182753
• Other study ID #: CS.P.12C
• Status: Recruiting
• Phase: Phase 3
• First received: August 12, 2010
• Last updated: August 16, 2010
• Start date: August 2010
• Est. completion date: August 2022

Study information

• Verified date: August 2010
• Source: Heidelberg University
• Contact: Anna V. Nikoghosyan, MD
• Phone: +496221568202
• Email: anna.nikoghosyan[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Health authority: Germany: Bundesamt für Strahlenschutz
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 154
• Est. completion date: August 2022
• Est. primary completion date: August 2022
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chondrosarcoma

Intervention

Radiation:
• carbon ion therapy
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.
• proton therapy
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.

Locations

Country	Name	City	State
Germany	University of Heidelberg	Heidelberg	Im neuenheimer Feld 400

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Country where clinical trial is conducted

Germany, 

References & Publications (6)

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. — View 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. — View 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. Review. — View Citation

Munzenrider JE, Liebsch NJ. Proton therapy for tumors of the skull base. Strahlenther Onkol. 1999 Jun;175 Suppl 2:57-63. Review. — View Citation

Schulz-Ertner D, Nikoghosyan A, Hof H, Didinger B, Combs SE, Jäkel 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. Epub 2006 Oct 23. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	Survival	Assessment of overall survival, progression free and metastasis free survival.	12 years	Yes
Secondary	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	Yes
Secondary	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