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Carbon Ion Radiotherapy for Primary Glioblastoma (CLEOPATRA)

Primary Purpose

Primary Glioblastoma

Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Carbon Ion Radiotherapy
Proton Radiotherapy
Sponsored by
University Hospital Heidelberg
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Glioblastoma focused on measuring Primary Glioblastoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University Hospital of Heidelberg, Department of Radiation Oncology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Experimental Arm

Standard Arm

Arm Description

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

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

Outcomes

Primary Outcome Measures

Overall Survival

Secondary Outcome Measures

Progression-free Survival
Toxicity
CTCAC 5.0

Full Information

First Posted
July 13, 2010
Last Updated
April 2, 2020
Sponsor
University Hospital Heidelberg
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1. Study Identification

Unique Protocol Identification Number
NCT01165671
Brief Title
Carbon Ion Radiotherapy for Primary Glioblastoma
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2018
Overall Recruitment Status
Completed
Study Start Date
July 2010 (Actual)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Hospital Heidelberg

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Glioblastoma
Keywords
Primary Glioblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental Arm
Arm Type
Experimental
Arm Description
Carbon Ion Radiotherapy to the Macroscopic Tumor 6 x 3 Gy E up to 18 Gy E
Arm Title
Standard Arm
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Radiation
Intervention Name(s)
Carbon Ion Radiotherapy
Intervention Description
Carbon ion Radiotherapy up to 18 Gy E in 3 Gy E fractions to the macroscopic tumor
Intervention Type
Radiation
Intervention Name(s)
Proton Radiotherapy
Intervention Description
Proton Radiotherapy up to 10 Gy E in 2 Gy E fractions to the macroscopic tumor
Primary Outcome Measure Information:
Title
Overall Survival
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Progression-free Survival
Time Frame
within 12 months
Title
Toxicity
Description
CTCAC 5.0
Time Frame
within 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
University Hospital of Heidelberg, Department of Radiation Oncology
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
20819220
Citation
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.
Results Reference
derived
Links:
URL
http://www.klinikum.uni-heidelberg.de/ro
Description
Homepage Department of Radiation Oncology

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Carbon Ion Radiotherapy for Primary Glioblastoma

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