New trial in Glioblastoma – step forward in the battle against an aggressive and incurable disease

Glioblastoma is a fast-growing malignant brain tumour that develops from glial cells which normally support the nerve cells within the brain. Glioblastoma is the most invasive and aggressive type of glial tumour, rapidly growing, commonly spreading into nearby brain tissue and considered incurable. In adults, glioblastoma occurs most often in the frontal and temporal lobes of the brain. As a highly aggressive and devastating disease, it results in death within the first 12 to 15 months after diagnosis in half of the patients.

The standard of care treatment for newly diagnosed glioblastomas is neurosurgery, followed by concurrent radiation and chemotherapy. Surgery reduces intracranial pressure from the tumour by removing as much of the solid tumour tissue as is safely possible. Following surgery, radiation therapy begins aiming at targeting the remaining tumour cells. Patients are also prescribed the chemotherapy drug temozolomide, to be taken every day during radiation therapy and then for up to 6 cycles after radiation (for 5 days – day one to day five – of each 28-day cycle). This combination treatment approach is called radiochemotherapy.

Because surgery, radiation and chemotherapy are unlikely to result in a durable control of tumor growth, investigators are looking for innovative new therapies during initial treatment and when first line therapy has failed.  Ongoing studies for glioblastoma assess novel drugs, gene therapy, and various types of immunotherapy.

EORTC, European Organisation for Research and Treatment of Cancer, in collaboration with the Canadian Cancer Trials Group and funding from Celgene Corporation are conducting a new trial, the EORTC-1709-BTG, which is a Phase III trial of marizomib in combination with standard temozolomide-based radiochemotherapy versus standard temozolomide-based radiochemotherapy alone in patients with newly diagnosed glioblastoma. Marizomib is a natural marine product, which has been shown in pre-clinical studies to rapidly cross the blood-brain barrier (BBB) and stop pathways that target proteins in the brain.

Marizomib has been tested in patients with newly diagnosed and recurrent glioblastoma in Phase I and Phase II studies. Based on encouraging observations from these Phase I/II trials of marizomib where it has been shown to have a manageable safety profile, a Phase III trial of marizomib in addition to standard of care in newly diagnosed glioblastoma has been launched (NCT02903069). The trial will establish whether the addition of marizomib to standard of care treatment has an impact on overall survival.

“The preliminary data on marizomib in glioblastoma seem very promising. To the medical community and glioblastoma patients worldwide the results of the Phase III trial will hopefully mean a groundbreaking step forward in the battle against a still highly aggressive and incurable disease,” said Maureen Vanlancker, Clinical Research Physician at EORTC HQ.

The trial will recruit 750 patients and is currently recruiting in 9 institutes in 6 countries.

“Marizomib is a promising drug because it has been shown to penetrate the blood-brain barrier,” said Dr Patrick Roth, Study Coordinator and Senior leading physician from University Hospital Zurich. “We are excited to assess the potential benefit of this novel drug in a large multi-center trial and hope that marizomib improves the prognosis of patients affected by glioblastoma.”

“Glioblastoma is an unrelenting, devastating disease,” said Kathy Oliver, Co-Director of international Brain Tumour Alliance.  “It has a dire prognosis and severely impacts on patients’ quality of life, creating substantial physical and cognitive disabilities and also frequently results in personality changes, loss of employment and significant psychosocial problems.  Glioblastoma also severely impacts on the caregivers’ and families’ lives as they struggle to cope with the many effects of the brain tumour on their loved one.”

“Given the extremely distressing challenges caused by glioblastoma, it’s crucial that we leave no stone unturned in our scientific investigations of potentially promising new therapies.  We look forward to following the progress of marizomib and its Phase III trial and hope that there may be positive results from this study which ultimately can bring some hope to our patient community.”