Open Access Study protocol

Randomised phase I/II study to evaluate carbon ion radiotherapy versus fractionated stereotactic radiotherapy in patients with recurrent or progressive gliomas: The CINDERELLA trial

Stephanie E Combs1*, Iris Burkholder2, Lutz Edler2, Stefan Rieken1, Daniel Habermehl1, Oliver Jäkel3, Thomas Haberer3, Renate Haselmann1, Andreas Unterberg4, Wolfgang Wick5 and Jürgen Debus1

Author Affiliations

1 Department of Radiation Oncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

2 Institute of Medical Biometry and Informatics, University of Heidelberg, Im Neuenheimer Feld 305, 69120 Heidelberg, Germany

3 Heidelberger Ionenstrahl Therapiezentrum (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany

4 Department of Neurooncology, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

5 Department of Neurosurgery, University Hospital of Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany

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BMC Cancer 2010, 10:533  doi:10.1186/1471-2407-10-533

Published: 6 October 2010

Abstract

Background

Treatment of patients with recurrent glioma includes neurosurgical resection, chemotherapy, or radiation therapy. In most cases, a full course of radiotherapy has been applied after primary diagnosis, therefore application of re-irradiation has to be applied cauteously. With modern precision photon techniques such as fractionated stereotactic radiotherapy (FSRT), a second course of radiotherapy is safe and effective and leads to survival times of 22, 16 and 8 months for recurrent WHO grade II, III and IV gliomas.

Carbon ions offer physical and biological characteristics. 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 increased 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 for the treatment of primary high-grade gliomas showed promising results in a small and heterogeneous patient collective.

Methods Design

In the current Phase I/II-CINDERELLA-trial re-irradiation using carbon ions will be compared to FSRT applied to the area of contrast enhancement representing high-grade tumor areas in patients with recurrent gliomas. Within the Phase I Part of the trial, the Recommended Dose (RD) of carbon ion radiotherapy will be determined in a dose escalation scheme. In the subsequent randomized Phase II part, the RD will be evaluated in the experimental arm, compared to the standard arm, FSRT with a total dose of 36 Gy in single doses of 2 Gy.

Primary endpoint of the Phase I part is toxicity. Primary endpoint of the randomized part II is survival after re-irradiation at 12 months, secondary endpoint is progression-free survival.

Discussion

The Cinderella trial is the first study to evaluate carbon ion radiotherapy for recurrent gliomas, and to compare this treatment to photon FSRT in a randomized setting using an ion beam delivered by intensity modulated rasterscanning.

Trial Registration

NCT01166308