Carbon Ion Radiotherapy for Primary Glioblastoma

NCT01165671 | Completed DMC

• 3 other identifiers: CLEOPATRA2009-014668-21ISRCTN37428883
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Primary Glioblastoma

Keywords

Primary Glioblastoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  12 months

Secondary Outcomes (2)

• Progression-free Survival

  within 12 months

• Toxicity

  within 12 months

Study Arms (2)

Experimental Arm

EXPERIMENTAL

Carbon Ion Radiotherapy to the Macroscopic Tumor 6 x 3 Gy E up to 18 Gy E

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

Radiation: Proton Radiotherapy

Interventions

Carbon Ion Radiotherapy RADIATION

Carbon ion Radiotherapy up to 18 Gy E in 3 Gy E fractions to the macroscopic tumor

Experimental Arm

Proton Radiotherapy RADIATION

Proton Radiotherapy up to 10 Gy E in 2 Gy E fractions to the macroscopic tumor

Standard Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• refusal of the patients to take part in the study
• 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.

Sponsors & Collaborators

• University Hospital Heidelberg: lead

Study Sites (1)

University Hospital of Heidelberg, Department of Radiation Oncology

Heidelberg, 69120, Germany

Location

Related Publications (1)

• 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.

  PMID: 20819220 DERIVED

Related Links

• Homepage Department of Radiation Oncology

MeSH Terms

Interventions

Heavy Ion Radiotherapy

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. Dr. Jürgen Debus

Study Record Dates

• First Submitted: July 13, 2010
• First Posted: July 20, 2010
• Study Start: July 1, 2010
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: April 3, 2020

Record last verified: 2018-05

Locations

DE (1)