Primary GlioblastomaCLEOPATRANCT01165671
Carbon Ion Radiotherapy for Primary Glioblastoma
A study testing Carbon Ion Radiotherapy and Proton Radiotherapy in people with Primary Glioblastoma, run by University Hospital Heidelberg at 1 site in Germany.
Trial summary
Treatment standard for patients with primary glioblastoma (GBM) is combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to a total dose of 60 Gy using photons. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Primary Glioblastoma
- What is being tested?
- Carbon Ion Radiotherapy and Proton Radiotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteGermany
- Study dates
- Jul 2010to Jan 2015
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- histologically confirmed unifocal, supratentorial primary glioblastoma
- macroscopic tumor after biopsy or subtotal resection
- indication for combined radiochemotherapy with temozolomide
- prior photon irradiation of 48-52 Gy to the T2-hyperintense area, resection cavity, areas of contrast enhancement adding 2-3cm safety margin in combination with standard temozolomide
- registration prior to photon RT or within photon RT allowing the beginning of particle therapy ≤ 4 days after completion of photon irradiation
- beginning of study treatment (proton or carbon ion RT) no later than 12 weeks after primary diagnosis
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- age ≥ 18 years
- Karnofsky Performance Score ≥ 60
- adequate contraception.
- Ability of subject to understand character and individual consequences of the clinical trial
- Written informed consent (must be available before enrolment in the trial)
Who cannot join
- refusal of the patients to take part in the study
- previous radiotherapy of the brain or chemotherapy with DTIC or TMZ other than during the radiochemotherapy stated in the inclusion criteria
- more than 52 Gy applied via photon-RT prior to particle therapy
- time interval of > 12 weeks after primary diagnosis (neurosurgical intervention) and beginning of study treatment (proton or carbon ion RT)
- Patients who have not yet recovered from acute toxicities of prior therapies
- Clinically active kidney, liver or cardiac disease
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- Known carcinoma < 5 years ago (excluding Carcinoma in situ of the cervix, basal cell carcinoma, squamous cell carcinoma of the skin) requiring immediate treatment interfering with study therapy
- Pregnant or lactating women
- Participation in another clinical study or observation period of competing trials, respectively.
Trial locations and contacts
1 site in 1 country.
Germany1 site
University Hospital of Heidelberg, Department of Radiation Oncology
Heidelberg, 69120
About this study
Official title: Randomized Phase II Study Evaluating a Carbon Ion Boost Applied After Combined Radiochemotherapy With Temozolomide Versus a Proton Boost After Radiochemotherapy With Temozolomide in Patients With Primary Glioblastoma
Treatment standard for patients with primary glioblastoma (GBM) is combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to a total dose of 60 Gy using photons. Using this treatment regimen, overall survival could be extended significantly however, median overall survival is still only about 15 months.
Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.
Read more
First Japanese Data on the evaluation of carbon ion radiation therapy showed promising results in a small and heterogeneous patient collective.
In the current Phase II-CLEOPATRA-Study a carbon ion boost will be compared to a proton boost applied to the macroscopic tumor after surgery at primary diagnosis in patients with GBM applied after standard radiochemotherapy with TMZ up to 50 Gy. In the experimental arm, a carbon ion boost will be applied to the macroscopic tumor up to a total dose of 18 Gy E in 6 fractions at a single dose of 3 Gy E. In the standard arm, a proton boost will be applied up to a total dose 10 Gy E in 5 single fractions of 2 Gy E.
Primary endpoint is overall survival, secondary objectives are progression-free survival, toxicity and safety.
Read the detailed description
Study design
The purpose of the trial is to compare a carbon ion boost to a proton boost delivered to the macroscopic tumor in combination with combined radiochemotherapy with TMZ in patients with primary GBM.
The aim of the study is to compare overall survival as a primary endpoint, and progression free survival, toxicity and safety as secondary endpoints.
Focus of the analysis is to evaluate the change in overall survival and local control by carbon ion radiotherapy. Therefore, the aim of the trial is to evaluate the improvement in outcome due to effect of the altered biology of carbon ions on GBM. Chemotherapy with TMZ is considered standard treatment and is administered continuously as it would be applied in standard patient care outside any trial.
Trial Design The trial will be performed as a single-center two-armed randomized Phase II study.
Patients fulfilling the inclusion criteria will be randomized into two arms:
Arm A - Experimental Arm Carbon Ion Radiation Therapy as a Boost to the macroscopic tumor Total Dose 18 Gy E, 6 fractions, 3 Gy E single dose
Arm B - Standard Arm Proton Radiation Therapy as a Boost to the macroscopic tumor Total Dose 10 Gy E, 5 fractions, 2 Gy E single dose
Standard chemotherapy with TMZ will be continued during the experimental and standard arm in conventional dosing of 75 mg/m2 per day.
- Conditions
- Primary Glioblastoma
- Being tested
- Carbon Ion Radiotherapy, Proton Radiotherapy
- Keywords
- Primary Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Carbon Ion RadiotherapyRadiation
Carbon ion Radiotherapy up to 18 Gy E in 3 Gy E fractions to the macroscopic tumor
Proton RadiotherapyRadiation
Proton Radiotherapy up to 10 Gy E in 2 Gy E fractions to the macroscopic tumor
| Study group | Role | What they receive |
|---|---|---|
| Experimental Arm | Experimental | Carbon Ion Radiotherapy to the Macroscopic Tumor 6 x 3 Gy E up to 18 Gy E Receives: Radiation: Carbon Ion Radiotherapy |
| Standard Arm | Active comparator | Proton Radiotherapy to the Macroscopic Tumor 5 x 2 Gy E up to 10 Gy E (Standard dose) applied after 48-52 Gy photon radiotherapy Receives: Radiation: Proton Radiotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival
Measured: 12 months
Secondary outcomes (2)
Progression-free Survival
Measured: within 12 months
Toxicity
CTCAC 5.0
Measured: within 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Primary GlioblastomaStudies of the same condition, open and under way.
- More trials run by University Hospital HeidelbergThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital Heidelberg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Juergen Debus, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01165671
- Sponsor's protocol ID
- CLEOPATRA
- Other IDs
- 2009-014668-21, ISRCTN37428883, 2009
- Acronym
- CLEOPATRA
- Status last verified
- May 2018
- First submitted
- 13 Jul 2010
- Last updated
- 3 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Combs SE, Kieser M, Rieken S, Habermehl D, Jakel O, Haberer T, Nikoghosyan A, Haselmann R, Unterberg A, Wick W, Debus J. Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial. BMC Cancer. 2010 Sep 6;10:478. doi: 10.1186/1471-2407-10-478.
PubMed 20819220
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase II Study Evaluating a Carbon Ion Boost Applied After Combined Radiochemotherapy With Temozolomide Versus a Proton Boost After Radiochemotherapy With Temozolomide in Patients With Primary Glioblastoma
- ClinicalTrials.gov ID
- NCT01165671
- Acronym / sponsor ID
- CLEOPATRA / CLEOPATRA
- Conditions
- Primary Glioblastoma
- Keywords
- Primary Glioblastoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- University Hospital HeidelbergUniversity, hospital or other
- Study start
- Jul 2010 (actual)
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 20 Jul 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.
Treatment standard for patients with primary glioblastoma (GBM) is combined radiochemotherapy with temozolomide (TMZ). Radiation is delivered up to a total dose of 60 Gy using photons. Using this treatment regimen, overall survival could be extended significantly however, median overall survival is still only about 15 months.
Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the GBM cell line as well as the endpoint analyzed. Protons, however, offer an RBE which is comparable to photons.
First Japanese Data on the evaluation of carbon ion radiation therapy showed promising results in a small and heterogeneous patient collective.
In the current Phase II-CLEOPATRA-Study a carbon ion boost will be compared to a proton boost applied to the macroscopic tumor after surgery at primary diagnosis in patients with GBM applied after standard radiochemotherapy with TMZ up to 50 Gy. In the experimental arm, a carbon ion boost will be applied to the macroscopic tumor up to a total dose of 18 Gy E in 6 fractions at a single dose of 3 Gy E. In the standard arm, a proton boost will be applied up to a total dose 10 Gy E in 5 single fractions of 2 Gy E.
Primary endpoint is overall survival, secondary objectives are progression-free survival, toxicity and safety.
Detailed description
Study design
The purpose of the trial is to compare a carbon ion boost to a proton boost delivered to the macroscopic tumor in combination with combined radiochemotherapy with TMZ in patients with primary GBM.
The aim of the study is to compare overall survival as a primary endpoint, and progression free survival, toxicity and safety as secondary endpoints.
Focus of the analysis is to evaluate the change in overall survival and local control by carbon ion radiotherapy. Therefore, the aim of the trial is to evaluate the improvement in outcome due to effect of the altered biology of carbon ions on GBM. Chemotherapy with TMZ is considered standard treatment and is administered continuously as it would be applied in standard patient care outside any trial.
Trial Design The trial will be performed as a single-center two-armed randomized Phase II study.
Patients fulfilling the inclusion criteria will be randomized into two arms:
Arm A - Experimental Arm Carbon Ion Radiation Therapy as a Boost to the macroscopic tumor Total Dose 18 Gy E, 6 fractions, 3 Gy E single dose
Arm B - Standard Arm Proton Radiation Therapy as a Boost to the macroscopic tumor Total Dose 10 Gy E, 5 fractions, 2 Gy E single dose
Standard chemotherapy with TMZ will be continued during the experimental and standard arm in conventional dosing of 75 mg/m2 per day.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental Arm | Experimental | Radiation: Carbon Ion RadiotherapyCarbon Ion Radiotherapy to the Macroscopic Tumor 6 x 3 Gy E up to 18 Gy E |
| Standard Arm | Active comparator | Radiation: Proton RadiotherapyProton Radiotherapy to the Macroscopic Tumor 5 x 2 Gy E up to 10 Gy E (Standard dose) applied after 48-52 Gy photon radiotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- histologically confirmed unifocal, supratentorial primary glioblastoma
- macroscopic tumor after biopsy or subtotal resection
- indication for combined radiochemotherapy with temozolomide
- prior photon irradiation of 48-52 Gy to the T2-hyperintense area, resection cavity, areas of contrast enhancement adding 2-3cm safety margin in combination with standard temozolomide
- registration prior to photon RT or within photon RT allowing the beginning of particle therapy ≤ 4 days after completion of photon irradiation
Key exclusion criteria (9 listed)
- refusal of the patients to take part in the study
- previous radiotherapy of the brain or chemotherapy with DTIC or TMZ other than during the radiochemotherapy stated in the inclusion criteria
- more than 52 Gy applied via photon-RT prior to particle therapy
- time interval of > 12 weeks after primary diagnosis (neurosurgical intervention) and beginning of study treatment (proton or carbon ion RT)
- Patients who have not yet recovered from acute toxicities of prior therapies
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 Ion RadiotherapyCarbon ion Radiotherapy up to 18 Gy E in 3 Gy E fractions to the macroscopic tumor | Radiation | Experimental Arm |
| Proton RadiotherapyProton Radiotherapy up to 10 Gy E in 2 Gy E fractions to the macroscopic tumor | Radiation | Standard Arm |
Primary outcome
Overall Survival
Time frame: 12 months
2 secondary outcomes
Progression-free Survival
Time frame: within 12 months
Toxicity
Time frame: within 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2020.
- Derived from this study: PubMed 20819220Combs SE, Kieser M, Rieken S, Habermehl D, Jakel O, Haberer T, Nikoghosyan A, Haselmann R, Unterberg A, Wick W, Debus J. Randomized phase II study evaluating a carbon ion boost applied after combined radiochemotherapy with temozolomide versus a proton boost after radiochemotherapy with temozolomide in patients with primary glioblastoma: the CLEOPATRA trial. BMC Cancer. 2010 Sep 6;10:478. doi: 10.1186/1471-2407-10-478.
- Homepage Department of Radiation OncologyLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Carbon Ion Radiotherapy and Proton Radiotherapy in people with Primary Glioblastoma, run by University Hospital Heidelberg 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 11 inclusion and 9 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: finished, as of the sponsor's last update on 3 Apr 2020. 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (time frame: 12 months). 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 NCT01165671, which also lists 1 linked publication.
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 3 Apr 2020.