ChordomaPhase 3HIT-1NCT01182779
Trial of Proton Versus Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base
A Phase 3 study testing Carbon ion and Protons in people with Chordoma and Tumor, run by Heidelberg University at 1 site in Germany.
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). Read more about this study
- Who is it for?
- Ages 18 to 80 years
- What is being tested?
- Carbon ion and Protons
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 319 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2010to Aug 2023
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University of Heidelberg
Heidelberg, 69120
Juergen Debus, MD, PhD
Anna V. Nikoghosyan, MD
About this study
Official title: Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-
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).
Read the 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.
- Being tested
- Carbon ion, Protons
- Keywords
- base of skull chordoma, radiation, carbon ions, protons
- Medical subject headings
- Chordoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbon ionRadiation
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.
ProtonsRadiation
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.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | 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. Receives: Radiation: Carbon ion |
| B | Active comparator | 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. Receives: Radiation: Protons |
What is being measured
The primary outcome is the main question the study is designed to answer.
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%.
Measured: 8-years
Secondary outcomes (3)
Survival
Assessment of overall survival, progression free and metastasis free survival.
Measured: 8-years
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.
Measured: 8 years
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.
Measured: 8 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Aug 2010 (estimated)
- Study startJul 2010
- Primary completionAug 2015 (estimated)
- Study completionAug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for ChordomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 319 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Investigators
- Juergen Debus, MD PhD, Principal investigator, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01182779
- Sponsor's protocol ID
- HIT-1
- Acronym
- HIT-1
- Status last verified
- Jul 2010
- First submitted
- 26 Jul 2010
- Last updated
- 17 Aug 2010
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 10394399Ares 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.
PubMed 19386442Hug 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.
PubMed 16734403Hug EB, Slater JD. Proton radiation therapy for chordomas and chondrosarcomas of the skull base. Neurosurg Clin N Am. 2000 Oct;11(4):627-38.
PubMed 11082173Weber 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.
PubMed 16168833Schulz-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.
PubMed 17363188Mizoe 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.
PubMed 19881902Nikoghosyan 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.
PubMed 21054824
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomised Trial of Proton vs. Carbon Ion Radiation Therapy in Patients With Chordoma of the Skull Base -Clinical Phase III Study-
- ClinicalTrials.gov ID
- NCT01182779
- Acronym / sponsor ID
- HIT-1 / HIT-1
- Keywords
- base of skull chordoma, radiation, carbon ions, protons
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 319 participants (estimated)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Aug 2015 (estimated)
- Study completion
- Aug 2023 (estimated)
- First posted
- 17 Aug 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Radiation: Carbon ionArm 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. |
| B | Active comparator | Radiation: ProtonsArm 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. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Carbon ionArm 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 | A |
| ProtonsArm 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 | B |
Primary outcome
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%.
3 secondary outcomes
Survival
Time frame: 8-years
Local control and patterns of recurrence
Time frame: 8 years
Toxicity
Time frame: 8 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2010.
- Background: PubMed 10394399Munzenrider JE, Liebsch NJ. Proton therapy for tumors of the skull base. Strahlenther Onkol. 1999 Jun;175 Suppl 2:57-63. doi: 10.1007/BF03038890.
- Background: PubMed 19386442Ares 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.
- Background: PubMed 16734403Hug 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.
- Background: PubMed 11082173Hug EB, Slater JD. Proton radiation therapy for chordomas and chondrosarcomas of the skull base. Neurosurg Clin N Am. 2000 Oct;11(4):627-38.
- Background: PubMed 16168833Weber 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.
- Background: PubMed 17363188Schulz-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.
- Background: PubMed 19881902Mizoe 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.
- Derived from this study: PubMed 21054824Nikoghosyan 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.
Related trials for Chordoma
Not yet recruitingObservational study
Clinical Genetics Branch Eligibility Screening Survey
Melanoma, Li-Fraumeni Syndrome
RecruitingObservational study
Children and Adults With Chordoma
Chordoma
Active, not recruitingObservational study
Genetic Clues to Chordoma Etiology: A Protocol to Identify Sporadic Chordoma Patients for Studies of Cancer-Susceptibility Genes
Genes, Sporadic Chordoma
RecruitingObservational study
Exploration of Personalized Biomarkers During Neoadjuvant Radiation Therapy for Spinal and Sacral Chordoma
Chordoma of Spine, Chordoma of Skull Base
Active, not recruiting
High Dose Intensity Modulated Proton Radiation Treatment +/- Surgical Resection of Sarcomas of the Spine, Sacrum and Base of Skull
Chordoma of Spine, Chordoma of Sacrum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Juergen Debus, MD PhD principal investigator
Heidelberg University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Carbon ion and Protons in people with Chordoma and Tumor, run by Heidelberg University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anna V. Nikoghosyan, MD (+496221568202, anna.nikoghosyan@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
local-progression free survival (LPFS) (time frame: 8-years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01182779, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2010.