Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Low and Inter-mediate Grade Chondrosarcoma of the Skull Base (CSP12C)

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

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.

Study Overview

• Status: Unknown
• Conditions: Chondrosarcoma
• Intervention / Treatment: Radiation: carbon ion therapy; Radiation: proton therapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 154
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Im neuenheimer Feld 400
    • Heidelberg, Im neuenheimer Feld 400, Germany, 69120
      • Recruiting
      • University of Heidelberg
      • Contact: Anna V. Nikoghosyan, MD; Phone Number: +49 6221 568202; Email: anna.nikoghosyan@med.uni-heidelberg.de
      • Contact: Rebecca Klumpp; Phone Number: +49 6221 5636902; Email: rebecca.klumpp@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: A; 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.	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.
ACTIVE_COMPARATOR: B; 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.	Radiation: 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.

What is the study measuring?

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 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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	Assessment of overall survival, progression free and metastasis free survival.	12 years
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
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

Collaborators and Investigators

• Sponsor: Heidelberg University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (ANTICIPATED): August 1, 2022
• Study Completion (ANTICIPATED): August 1, 2022

Study Registration Dates

• First Submitted: August 12, 2010
• First Submitted That Met QC Criteria: August 16, 2010
• First Posted (ESTIMATE): August 17, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): August 17, 2010
• Last Update Submitted That Met QC Criteria: August 16, 2010
• Last Verified: August 1, 2010

More Information

Terms related to this study

• Keywords: Radiation; Chondrosarcoma; carbon ion
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Sarcoma; Chondrosarcoma
• Other Study ID Numbers: CS.P.12C