Related Experiment Video
Updated: Mar 22, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Phase I trial of dovitinib (TKI258) in recurrent glioblastoma
Niklas Schäfer1,2, Gerrit H Gielen3, Sied Kebir1,2
1Division of Clinical Neurooncology, Department of Neurology, Medical Center Bonn, 53127, Bonn, Germany.
Purpose:
Dovitinib (TKI258) is an oral multi-tyrosine kinase inhibitor of FGFR, VEGFR, PDGFR β, and c-Kit. Since dovitinib is able to cross the blood-brain barrier and targets brain tumor-relevant pathways, we conducted a phase I trial to demonstrate its safety in recurrent glioblastoma (GBM).
Patients And Methods:
Patients with first or second GBM recurrence started treatment with the maximal tolerated dose (MTD) previously established in systemic cancer patients (500 mg/d, 5 days on/2 days off). A modified 3 + 3 design in three cohorts (500, 400, 300 mg) was used.
Results:
Twelve patients were enrolled. Seventy-two adverse events (AEs) occurred and 16.7 % of AEs were classified as ≥CTC grade 3 toxicity, mainly including hepatotoxicity and hematotoxicity. Only one out of six patients of the 300-mg cohort showed grade 3 toxicity. The PFS-6 rate was 16.7 %, and it was not associated with detection of the FGFR-TACC gene fusion in the tumor.
Conclusion:
Dovitinib is safe in patients with recurrent GBM and showed efficacy in only some patients unselected for target expression. The recommended phase II dose of 300 mg would be substantially lower than the recently established MTD in systemic cancer patients. Further personalized trials are recommended.
Insights
Dovitinib is safe for recurrent glioblastoma (GBM) patients. A lower dose (300 mg) is recommended for Phase II trials, showing potential efficacy in some patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Dovitinib (TKI258) is a multi-tyrosine kinase inhibitor targeting FGFR, VEGFR, PDGFR β, and c-Kit.
- It crosses the blood-brain barrier, making it a candidate for brain tumor treatment.
Purpose of the Study:
- To evaluate the safety and tolerability of dovitinib in patients with recurrent glioblastoma (GBM).
- To determine a recommended Phase II dose for dovitinib in this patient population.
Main Methods:
- A Phase I trial using a modified 3+3 design enrolled 12 patients with recurrent GBM.
- Patients received dovitinib at doses of 500 mg, 400 mg, or 300 mg daily (5 days on/2 days off).
Main Results:
- The most common adverse events (AEs) were hepatotoxicity and hematotoxicity, with 16.7% of AEs being Grade 3 or higher.
- Only one patient in the 300 mg cohort experienced Grade 3 toxicity.
- The 6-month progression-free survival (PFS-6) rate was 16.7%.
Conclusions:
- Dovitinib demonstrates safety in recurrent GBM patients.
- A recommended Phase II dose of 300 mg is proposed, which is lower than the established MTD in other cancers.
- Further personalized trials are warranted to optimize treatment based on target expression.
Related Concept Videos
02:56Treatment Resistent Cancers
02:56Treatment Resistant Cancers
01:11Clinical Trials: Overview
01:16Clinical Trials
There are four phases in a clinical trial. A phase one...