Carbon Ion Radiotherapy for Recurrent Gliomas (CINDERELLA)

University Hospital Heidelberg

Status

Completed

Conditions

Glioma

Treatments

Radiation: Carbon Ion Radiotherapy

Radiation: Fractionated Stereotactic Radiotherapy (FSRT)

Study type

Interventional

Funder types

Other

Identifiers

NCT01166308

2009-017352-26 (EudraCT Number)

CINDERELLA

Details and patient eligibility

About

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 cautiously. 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 tumors.

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 increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the Glioblastoma (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.

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.

Enrollment

56 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

unifocal, supratentorial recurrent glioma
contrast enhancement on T1-weighted MRI and/or Amino-Acid-PET-positive high-grade tumor areas
indication re-irradiation
age ≥ 18 years of age
Karnofsky Performance Score ≥60
For women with childbearing potential, (and men) 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

Multifocal Glioma or Gliomatosis cerebri
refusal of the patients to take part in the study
previous re-irradiation or prior radiosurgery or prio treatment with interstitial radioactive seeds
time interval of < 6 months after primary radiotherapy
Patients who have not yet recovered from acute toxicities of prior therapies
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.