Study on the Treatment of Glioblastomas: Investigation of the Combination of Radiochemotherapy and the Drug Bevacizumab (VEGF Inhibitor)

Glioblastoma is the most common primary malignant brain tumor in adults and has a very poor prognosis. The current standard of care consists of surgery, radiation therapy, and chemotherapy with temozolomide. The treatment cannot cure the tumor, but it can prolong survival. Glioblastoma is difficult to treat because it grows rapidly and diffusely into surrounding brain tissue, making it hard to delineate and remove. The cancer cells are also genetically very diverse, which means that not all cells respond equally to treatment. Treatment often kills only a portion of the cells, while others survive and continue to grow. As a result, even after intensive treatment, a new tumor usually forms within just a few months. Another problem is the brain’s natural protective barrier; because of it, many drugs cannot reach the tumor in sufficient quantities. As a result, many conventional cancer therapies are less effective against glioblastoma. For these reasons, intensive research is currently underway to identify new treatment options that can improve patients’ chances of survival.

The goal of the PRIDE study is to investigate whether the combination of chemoradiotherapy—despite an escalation of the radiation dose—with concomitant bevacizumab administration is just as safe for treating glioblastoma and may offer advantages over standard treatment. In isotoxic dose escalation, the radiation dose is adjusted to the individual tolerance of the surrounding healthy tissues (known as organs at risk, OAR) rather than using a uniform radiation dose for all patients. The goal is to administer the highest possible radiation dose without disproportionately increasing the risk of side effects—tailored individually for each patient. The aim is to identify the most effective dose that can still be safely administered. This allows for more effective treatment of the tumor. Bevacizumab is a medication that inhibits vascular endothelial growth factor (VEGF) and thereby suppresses the formation of new blood vessels in the tumor. The combination of radiation therapy with bevacizumab is used to counteract potential side effects caused by the higher radiation dose and thus potentially improve the efficacy and tolerability of the tailored treatment plan. Bevacizumab is not yet approved in Germany for the treatment of glioblastoma. In this study, all participating patients receive a combination of radiation therapy and chemotherapy with isotoxic dose escalation and concomitant VEGF inhibition with bevacizumab. Radiotherapy and chemotherapy last a total of six weeks, with bevacizumab administered twice, three weeks apart. Approximately six weeks after completion of treatment, maintenance therapy with the chemotherapeutic agent temozolomide begins for six cycles as part of standard treatment. All patients are monitored for the first time four to six weeks after chemoradiotherapy and subsequently every three months via clinical examination and cranial MRI. The primary endpoint of the study is disease-free survival and overall survival two years after enrollment.

Patients between the ages of 18 and 70 with confirmed IDH wild-type, MGMT-unmethylated glioblastoma are eligible to participate in this study. Patients with previously treated glioblastoma, other active cancers, or severe comorbidities are excluded. Participation in the study is also not possible if a magnetic resonance imaging (MRI) scan of the head is not feasible.