Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base

Tumor Clinical Trial

— HIT-1  

Official title:

Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01182779
• Other study ID #: HIT-1
• Status: Recruiting
• Phase: Phase 3
• First received: July 26, 2010
• Last updated: August 16, 2010
• Start date: July 2010
• Est. completion date: August 2023

Study information

• Verified date: July 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" (German Radiation Protection Authority)
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 319
• Est. completion date: August 2023
• Est. primary completion date: August 2015
• 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 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.

Study Design

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

Related Conditions & MeSH terms

• Chordoma
• Treatment
• Tumor

Intervention

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.
• 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.

Locations

Country	Name	City	State
Germany	University of Heidelberg	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Country where clinical trial is conducted

Germany, 

References & Publications (7)

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, 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

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. Review. — View Citation

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. — 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, Karger CP, Feuerhake A, Nikoghosyan A, Combs SE, Jäkel 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. Epub 2007 Mar 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 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%.	8-years	No
Secondary	Survival	Assessment of overall survival, progression free and metastasis free survival.	8-years	No
Secondary	Local control and patterns of recurrence	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.	8 years	No
Secondary	Toxicity	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.	8 years	No