Multiple Drug Therapy for Glioblastoma

This trial explores several new drugs to treat glioblastoma, an aggressive brain cancer. The aim is to evaluate the effectiveness of these drugs, either alone or in combination, in slowing or stopping cancer growth. Participants will receive radiation treatment along with medications such as Temozolomide (a chemotherapy drug), Neratinib (a targeted therapy drug), or QBS10072S (an experimental treatment). This trial suits those diagnosed with glioblastoma or gliosarcoma who have not yet received radiation or chemotherapy. Participants must be able to swallow pills and plan to start radiation therapy within a specific time after surgery.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in glioblastoma treatment.

Participants must stop taking enzyme-inducing anti-epileptic drugs and drugs that are strong inhibitors or inducers of the CYP3A enzyme at least 7 days before starting the study. Herbal medications and certain citrus fruits should also be avoided. If you are on these medications, you will need to stop them before joining the trial.

A previous study found Temozolomide, one of the drugs being tested, safe for treating brain tumors, and the FDA has already approved it for this purpose. This approval indicates thorough research and general safety for many patients.

Research has shown that Neratinib was mostly well-tolerated in trials. Some participants reported side effects, but these were similar to previously observed effects with this drug, with no new or unexpected issues.

For QBS10072S, early findings suggest it was well-tolerated by patients with a specific type of glioblastoma (a kind of brain cancer) when used with radiation therapy. Most patients did not experience severe or unexpected side effects.

Conversely, CC-115 showed higher risks. Studies reported significant side effects in many patients, raising concerns about its safety, indicating it might not be suitable for everyone.

Researchers are excited about these treatments for glioblastoma because they offer new ways to tackle this aggressive brain cancer. Unlike standard treatments that focus mainly on Temozolomide and radiation, Abemaciclib is a CDK4/6 inhibitor that targets cancer cell cycle progression, potentially stopping tumor growth. Neratinib is an irreversible tyrosine kinase inhibitor, which might block signals that glioblastoma cells use to grow. QBS10072S is distinctive because it's being tested to work in synergy with radiation, which could enhance the effectiveness of existing treatments. These novel approaches offer hope for more effective interventions against a cancer that has been notoriously hard to treat.

Research has shown that Temozolomide, which participants in this trial may receive, is FDA-approved for treating glioblastoma and has been effective for this condition. In this trial, some participants will receive a combination of Abemaciclib and Temozolomide. Previous studies showed an average survival of 16 months, with 58% living for at least one year, indicating a possible benefit. Another group will receive Neratinib with Temozolomide, which has significantly extended the time patients live without disease progression, especially in those with the EGFR-positive tumor marker. QBS10072S, a new treatment option in this trial, slowed tumor growth in early studies and was well-tolerated when combined with radiation in glioblastoma patients. These findings support further exploration of these drugs for glioblastoma treatment.¹²³⁶⁷