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Clinical Trial
. 2010 Oct 6:10:533.
doi: 10.1186/1471-2407-10-533.

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 Combs  1 , Iris Burkholder, Lutz Edler, Stefan Rieken, Daniel Habermehl, Oliver Jäkel, Thomas Haberer, Renate Haselmann, Andreas Unterberg, Wolfgang Wick, Jürgen Debus
Affiliations
Clinical Trial

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 Combs et al. BMC Cancer. .

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.

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Figures

Figure 1
Figure 1
Flow Chart of the Cinderella-Study.
Figure 2
Figure 2
Typical treatment plan for carbon ion radiotherapy for a patients with a recurrent glioblatoma. Treatment is performed using the Siemens TPS for particle therapy, target volume delienation is based on CT- and MR-imaging with contrast enhancement.
See this image and copyright information in PMC

References

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