Carbon Ion Radiotherapy for Primary Glioblastoma

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.

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.