- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01182779
Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base (HIT-1)
Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-
Study Overview
Status
Intervention / Treatment
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 Type
Enrollment (Anticipated)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
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Heidelberg, Germany, 69120
- Recruiting
- University of Heidelberg
-
Principal Investigator:
- Juergen Debus, MD, PhD
-
Sub-Investigator:
- Anna V. Nikoghosyan, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
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 - 63 Gy E ± 5%, further 5-7 fractions a 3 Gy E. |
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. |
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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%.
|
8-years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Survival
Time Frame: 8-years
|
Assessment of overall survival, progression free and metastasis free survival.
|
8-years
|
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.
|
8 years
|
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.
|
8 years
|
Collaborators and Investigators
Sponsor
Publications and helpful links
General 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HIT-1
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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