Work packages
6. August, 21

WP14 – Selection of targeted therapies and allocation of patients to clinical trial


Designing clinical trials where the right drugs are given to the right patients is critical for improving the likelihood of effect form targeted treatments in glioblastoma. Gliotarget, a Danish nationwide clinical trial was designed having this in mind. 


With the advances of sequencing technology, the understanding of cancer at the molecular level has improved in recent years. Frequent genomic alterations causing cancer has been identified and treatment targeting these alterations has emerged across several tumor types. In tumor types such as breast cancer, colorectal cancer and non-small cell lung cancer, targeted treatment based on identification of genomic alterations is now standard. However, regarding Glioblastoma, no broadly applicable targeted treatments have been able to prolong overall survival.

There are multiple aspects that might explain the limited success in treating glioblastoma with targeted treatments. One of the aspects, is the rare use of biomarker enrichment in glioblastoma trials. The targeted therapies have mostly been studied in unselected patient populations, thus limiting the likelihood of response. Most trials performed in glioblastoma have also largely been in the relapse setting where the inherent poor prognosis of glioblastoma might conceal the drug efficacy. Finally, there has been a lack of knowledge regarding prognostic factors essential in the stratification of patients. 

In this project, we have recognized and addressed the current limitations, and therefore have the potential to improve the treatment of Glioblastoma.


  • Design and implement Gliotarget, a Danish nationwide phase I/II platform trial 
  • Examine if individualized treatment, in the first line setting, targeting specific molecular alterations improve the survival of patients with glioblastoma


Gliotarget is a biomarker enriched phase I/II platform trial with initially 4 predefined biomarker selected arms, one miscellaneous biomarker arm and one control arm.  All patients receive standard therapy with concomitant radiochemotherapy and adjuvant Temozolomide. The experimental treatment is given alongside the adjuvant Temozolomide. Molecular analysis, including Whole Genome Sequencing, is performed on all patients, to identify actionable biomarkers. The miscellaneous arm gathers patients with not previously defined biomarkers upon which the weekly molecular tumor board decides to treat. 

Gliotarget includes newly diagnosed IDH-wt glioblastoma patients. In addition, to exclude the patients where the inherent poor prognosis might conceal the drug efficacy, the patients must have a 50% probability of being alive 12 months after initial surgery, according to a prognostic model developed in our institution.

The sample size is calculated with Simon’s two-stage design using treatment effect at 9-months progression free survival (PFS9). We anticipate 9 patients for stage one and 24 in total, for each arm. Treatment effect is defined as 65% of the patients in an experimental arm reaching PFS9. For the survival analysis, supplementing the control arm data with leveraged external controls taken from our prospectively registered database will decrease the probability of false positive results. 

Expected outcome 

Gliotarget provides a platform for assessing drug efficacy in a timely and cost-efficient manner and grants Danish glioblastoma patients access to potentially life-prolonging targeted treatments. 

The chosen biomarkers and treatments will be presented when confirmed.