The investigational drug 5-ALA (known under the trade name Gliolan®) is an approved drug for the surgical removal of malignant glioma (WHO grade III and IV). In this trial, the drug is being tested outside of its actual approval as a radiosensitizer in combination with conventional radiotherapy for first-time recurrence (relapse) of malignant glioma. In this clinical trial, the investigational drug 5-ALA is being used for the first time in a multiple dose escalation regimen in combination with radiotherapy following surgical removal of a recurrent malignant glioma in humans. The investigational drug, 5-ALA, has been used as a single dose to date as a standard of care for visualization of malignant tissue in the surgical removal of gliomas. The planned clinical trial will first and foremost investigate how well repeated administration of the investigational drug 5-ALA is tolerated in combination with radiotherapy. At the same time, the design of the trial serves to optimize this novel therapeutic procedure with regard to the frequency of administration of the investigational drug 5-ALA in combination with radiotherapy for future clinical trials. As a secondary objective, the efficacy of additional 5-ALA administration will also be investigated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
A repetitive dose of Gliolan will be administrated in combination with radiotherapy (radiodynamic therapy)
Radiotherapy will be performed in combination with Gliolan administration
University Hospital Münster, Klinik für Neurochirurgie
Münster, Germany
RECRUITINGMaximum tolerated dose (MTD)
In the resent study we will investigate the maximum-tolerated dose (MTD) of the combination of 5-ALA and radiation. MTD is defined as the highest number of RDT that does not cause unacceptable side effects, i.e. at which no more than 1 of 6 patients suffers a dose-limiting toxicity (DLT). DLT describes side effects of a drug that are serious enough to prevent an increase of dose (NCI dictionary of cancer terms). In the present study it is defined as any ≥ Gr.3 hematological toxicity, any ≥ Gr.3 neurological toxicity and any ≥ Gr.3 non-hematological toxicity occurring during the 6 week observation period, that does not resolve to pre-treatment baseline or ≤ Gr. 2 within 3 weeks, either spontaneously or with adequate treatment. To detect any relevant DLT the following aspects are monitored: * Toxicological safety of repeat doses of 5-ALA * Neurological safety of RDT * Dermatological safety of RDT * Assess all new AEs CTCAE grade 2 or higher
Time frame: 6 weeks after last R(D)T in adjuvant phase
Overall survival rate (OSR)
Percentage of patients who are alive 6 months after first R(D)T
Time frame: 6 months after first R(D)T in adjuvant phase
progression-free survival rate (PFS)
Percentage of patients without tumor progression 6 months after first R(D)T in adjuvant phase
Time frame: 6 months after first R(D)T in adjuvant phase
event-free survival rate (EFS)
Percentage of patients without suffering any disease related event such as DLT or progression until 6 months after inclusion
Time frame: 6 months after inclusion
concentration changes of immunhistochemistry marker (e.g. Caspase-3, IBA1, H&E, EvG, P53, Ki 67, gammaH2AX)
analytic results of pharma-radio-dynamic tissue changes. Tissue samples collected during surgery of cohort 0 and 1
Time frame: during surgery
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