Phase I/IIa Study of Concomitant Radiotherapy With Olaparib and Temozolomide in Unresectable High Grade Gliomas Patients

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HGGs are the most common and most aggressive primary brain tumor. There is a real need to improve care management of GBM patients. Attempts to achieve cure by increasing radiation dose result in unacceptable neurotoxicity. As for radiosensitizers, they can exacerbate normal tissue damage. Since GBM ...

HGGs are the most common and most aggressive primary brain tumor. There is a real need to improve care management of GBM patients. Attempts to achieve cure by increasing radiation dose result in unacceptable neurotoxicity. As for radiosensitizers, they can exacerbate normal tissue damage. Since GBM represent a rapidly dividing cell population within the nonreplicating normal brain, the therapeutic ratio may be enhanced by specific radiosensitization of proliferating cells. Resistance to apoptosis is a paramount issue in the treatment of HGG. Targeting PARP by the inhibitors like olaparib can reduce proliferation and lowers the apoptotic threshold of HGG (effect showed in vivo and in vitro). In this context, we propose a phase I-IIa trail to investigate the toxicity and efficacy of olaparib and TMZ concomitantly with radiotherapy in first line treatment of unresectable high risk HGG. Correlation between treatment response and tumor profiling will allow us to identify biomarkers that can be useful in treatment improvement and/or present a prognostic value. Then, the transfer of this approach will be evaluated in terms of compatibility with the requirements of diagnostic.

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