Brussels - Glioblastoma (GBM) is an aggressive type of brain cancer that escapes most drug treatments. To tackle this issue, a treatment regimen with 9 different drugs in addition to low-dose, continuous chemotherapy, was devised. The first results of this exceptional trial are promising.

For decades, new experimental therapies have repeatedly failed to improve the outcome of patients relapsing after the first treatment of glioblastoma. In 2013, Prof. Marc-Eric Halatsch and Dr. Richard Kast suggested that these repeated failures were due to the capability of this type of brain cancer to escape the action of one single treatment.

With input from other researchers, they proposed a new, out-of-the box concept to treat patients with glioblastoma called ‘Coordinated Undermining of Survival Paths’ (CUSP). The CUSP concept attempts to block multiple growth-driving mechanisms of the tumour leading to its survival.

From 1 to 10

To identify the drugs that could qualify, the researchers investigated the scientific literature and an intense sifting process led to the selection of 9 non-cancer drugs, already on the market. Hence the name of the trial, CUSP9.

In this ‘proof of concept’ clinical trial 9 patients were treated with the 9 drugs simultaneously, in addition to temozolomide (chemotherapy) twice daily.

“I was amazed when the trial finally got approved by the health authorities. To me, it proves that no idea is ever too bold to be tried in such devastating diseases as brain cancer”, said Kristine Beckers, Trial Manager of the Anticancer Fund.

The role of the Anticancer Fund was instrumental. We initiated the project, assisted the researchers during the whole process and provided funding for this trial. Glioblastoma is one of the most difficult tumours to treat and we believe it’s our duty to address the unmet need here. We are convinced that combining existing drugs might be a solution.

Safety first

As a 10-drug clinical trial was unprecedented, the very first objective was to assess the safety of the treatment.

In December 2020, the study was completed, and the treatment turned out to be safe and generally well-tolerated in all 9 patients, though modifying the dose of some drugs was needed because of side effects.

This trial proves that carrying out a complex trial with 10 different drugs is feasible. Where science justifies it, researchers should be encouraged to set up trials with multi-drug combinations, to address the complex nature of cancer.

Because this study was done in only a small number of patients, any interpretation about the effectiveness of the CUSP9v3 regimen is not possible. For that, a follow-up trial in a larger number of patients will be set up.

“I’m really proud we did move this concept to an actual trial. It took huge efforts and perseverance from all of us involved. What we now get is a steppingstone that anyone can use in support of trials of rational multi-drug combinations. I have great hopes that some of these scientifically-determined combinations will eventually prove effective”, concluded Gauthier Bouche, Director of Clinical Research of the Anticancer Fund.

Read more about the CUSP9v3-trial

Discover the scientific publication in Neuro-Oncology Advances

Learn more about drug repurposing