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

• ClinicalTrials.gov Identifier: NCT01182779
• Recruitment Status: Recruiting
• First Posted: August 17, 2010
• Last Update Posted: August 17, 2010
• Sponsor: Heidelberg University
• Information provided by: Heidelberg University

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Chordoma; Tumor; Treatment	Radiation: Carbon ion; Radiation: Protons	Phase 3

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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 319 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-
• Study Start Date: July 2010
• Estimated Primary Completion Date: August 2015
• Estimated Study Completion Date: August 2023

Arms and Interventions

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 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E.	Radiation: Carbon ion; 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.
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, 28 fractions Total dose to the PTV1 - 72 Gy E ± 5%, further 6-9 fractions a 2 Gy E.	Radiation: Protons; 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.

Outcome Measures

Primary Outcome Measures :

1. local-progression free survival (LPFS) [ Time Frame: 8-years ]
   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 LPFS defined as time from the randomisation to observed local reccurrence or death from any cause in the absence of documented local disease progression. Lo-cal recurrence defined as MRT or CT - morphological tumor progress in the former irradiated region. A 10% increase in the LPFS is considered clinically relevant as-suming that the LPFS rate for the proton therapy is 70%.

Secondary Outcome Measures :

1. Survival [ Time Frame: 8-years ]
   Assessment of overall survival, progression free and metastasis free survival.
2. Local control and patterns of recurrence [ Time Frame: 8 years ]
   Local recurrences will be confirmed radiologically and histologically whenever possible. At least two medical doctors (radiation oncologist and/or radiologist) will be required to judge of the recurrence.
3. Toxicity [ Time Frame: 8 years ]
   Acute and late toxicity will be analysed due to Common Terminology Criteria for Adverse Events: CTCAE V4.0 for acute reaction and RTOG/EORTC for late effects.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Anna V. Nikoghosyan, MD; +496221568202; anna.nikoghosyan@med.uni-heidelberg.de

Contact: Juergen Debus, MD, PhD; +496221568202; juergen.debus@med.uni-heidelberg.de

Locations

Germany

University of Heidelberg; Recruiting

Heidelberg, Germany, 69120

Principal Investigator: Juergen Debus, MD, PhD

Sub-Investigator: Anna V. Nikoghosyan, MD

Sponsors and Collaborators

Heidelberg University

Investigators

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

More Information

Publications:

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. Review of skull base chordomas: prognostic factors and long-term results of proton-beam radiotherapy. Neurosurg Focus. 2001 Mar 15;10(3):E11. doi: 10.3171/foc.2001.10.3.12.

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.

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.

Schulz-Ertner D, Karger CP, Feuerhake A, Nikoghosyan A, Combs SE, Jakel O, Edler L, Scholz M, Debus J. Effectiveness of carbon ion radiotherapy in the treatment of skull-base chordomas. Int J Radiat Oncol Biol Phys. 2007 Jun 1;68(2):449-57. doi: 10.1016/j.ijrobp.2006.12.059. Epub 2007 Mar 23.

Mizoe JE, Hasegawa A, Takagi R, Bessho H, Onda T, Tsujii H. Carbon ion radiotherapy for skull base chordoma. Skull Base. 2009 May;19(3):219-24. doi: 10.1055/s-0028-1114295.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nikoghosyan AV, Karapanagiotou-Schenkel I, Munter MW, Jensen AD, Combs SE, Debus J. Randomised trial of proton vs. carbon ion radiation therapy in patients with chordoma of the skull base, clinical phase III study HIT-1-Study. BMC Cancer. 2010 Nov 5;10:607. doi: 10.1186/1471-2407-10-607.

• Responsible Party: Juergen Debus, MD PhD, Dept. of Radiation Oncology, INF 400, 69120 Heidelberg, University of Heidelberg
• ClinicalTrials.gov Identifier: NCT01182779
• Other Study ID Numbers: HIT-1
• First Posted: August 17, 2010
• Last Update Posted: August 17, 2010
• Last Verified: July 2010

Keywords provided by Heidelberg University:

base of skull chordoma; radiation; carbon ions; protons

Additional relevant MeSH terms:

Chordoma; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms