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

• ClinicalTrials.gov Identifier: NCT01182753
• Recruitment Status: Unknown
• First Posted: August 17, 2010
• Last Update Posted: August 17, 2010
• Sponsor: Heidelberg University
• Information provided by: Heidelberg University

Tracking Information

• First Submitted Date: August 12, 2010
• First Posted Date: August 17, 2010
• Last Update Posted Date: August 17, 2010
• Study Start Date: August 2010
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 16, 2010)

Local-Progression Free Survival (LPFS) [ Time Frame: 5 years ]

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%.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 16, 2010)

• Survival [ Time Frame: 12 years ]
  Assessment of overall survival, progression free and metastasis free survival.
• Toxicity [ Time Frame: 12 years ]
  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.
• Patterns of recurrence and local control rate [ Time Frame: 5 years ]
  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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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.

• 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.

Study Arms

• 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.

  Intervention: Radiation: carbon ion therapy
• 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.

  Intervention: Radiation: proton therapy

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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 16, 2010): 154
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 2022
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Germany

Administrative Information

• NCT Number: NCT01182753
• Other Study ID Numbers: CS.P.12C
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Prof. Dr. Dr. J. Debus, University of Heidelberg
• Original Responsible Party: Same as current
• Current Study Sponsor: Heidelberg University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Juergen Debus, MD PhD; Heidelberg University

• PRS Account: Heidelberg University
• Verification Date: August 2010