Carbon Ion Radiotherapy for Primary Glioblastoma

Primary Glioblastoma Clinical Trial

— CLEOPATRA  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01165671
• Other study ID #: CLEOPATRA
• Secondary ID: 2009-014668-21IS
• Status: Completed
• Phase: N/A
• Start date: July 2010
• Est. completion date: January 2015

Study information

• Verified date: May 2018
• Source: University Hospital Heidelberg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

• 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)

Exclusion Criteria:

• 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

• 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.

Related Conditions & MeSH terms

• Glioblastoma
• Primary Glioblastoma

Intervention

Radiation:
• Carbon Ion Radiotherapy
Carbon ion Radiotherapy up to 18 Gy E in 3 Gy E fractions to the macroscopic tumor
• Proton Radiotherapy
Proton Radiotherapy up to 10 Gy E in 2 Gy E fractions to the macroscopic tumor

Locations

Country	Name	City	State
Germany	University Hospital of Heidelberg, Department of Radiation Oncology	Heidelberg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival		12 months
Secondary	Progression-free Survival		within 12 months
Secondary	Toxicity	CTCAC 5.0	within 12 months

External Links

•   Homepage Department of Radiation Oncology