Dovitinib (TKI258) in the Treatment of Patients With Relapsed Glioblastoma (TKI258)
|ClinicalTrials.gov Identifier: NCT01972750|
Recruitment Status : Unknown
Verified April 2016 by PD Dr. Martin Glas, University Hospital, Bonn.
Recruitment status was: Active, not recruiting
First Posted : October 30, 2013
Last Update Posted : April 19, 2016
|Condition or disease||Intervention/treatment||Phase|
|First or Second Recurrence of Glioblastoma||Drug: Dovitinib||Phase 1|
Despite intensive treatment efforts combining surgery, radio- and chemotherapy, the prognosis of patients suffering from glioblastoma (GBM) remains poor. Virtually all GBMs progress despite therapy. Patients receiving the standard therapy at primary disease have a median overall survival of 12-15 months. There is currently no defined standard treatment regimen for recurrent GBM. Tyrosine kinase receptor-targeted therapy is widely used in preclinical and clinical experimental brain tumor research. Increased tyrosine kinase activity has been asssociated with GBM oncogenesis and several tyrosine kinase receptors, e.g. VEGFR, FGFR, PDGFR are upregulated in malignant glioma. In the past and in the present, targeting of VEGF- and PDGF-signaling (amongst others) has shown promising preclinical and clinical results in human glioblasto-ma.
In that context our own in vitro studies lead to the assumption that application of a multi-targeted tyrosine kinase inhibitor could be a most effective treatment approach for GBM patients. We were able to demonstrate that GBM cells from different tumor regions express different set of tyrosine kinase receptors that all could be targeted by the multi-targeted tyrosine kinase inhibitor TKI258, including PDGFRß, CSF 1R, KIT, FLT3, VEGFR, TrkA, RET and FGFRs. In combination with its ability to cross the blood-brain-barrier (BBB), the exploration of TKI258 for patients with recurrent GBM appears very promising.
Recently, safety and feasibility of TKI258 was demonstrated in adult patients with advanced solid malignan-cies. The maximum tolerated dose (MTD) was determined and a recommended dose for phase II trials was established. Meanwhile, TKI258 is in phase III development in renal cell carcinoma, and in phase II devel-opment in advanced breast cancer, relapsed multiple myeloma and urothelial cancer.
Since the toxicity profile for compounds that could cross the BBB might be different in patients with CNS diseases/disorders (e.g. brain tumors) compared to patients with malignancies outside the CNS, we here propose a phase I trial exploring TKI258 in patients with recurrent glioblastoma.
In this study with a modified 3+3 dose finding design, a safe and tolerable dose of TKI258 in patients with relapsed glioblastoma should be established.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Multi-targeted Tyrosine Kinase Inhibitor Dovitinib (TKI258) in the Treatment of Patients With Relapsed Glioblastoma|
|Study Start Date :||October 2013|
|Estimated Primary Completion Date :||November 2016|
|Estimated Study Completion Date :||November 2016|
IMP: Dovitinib (TKI258) Manufacturer: Novartis Dose: 500 mg/day Mode of application: orally Duration of treatment: 5 days / week (5 days on / 2 days off) of a 28-days cycle until progression of disease
daily oral intake of capsule
Other Name: TKI258
- safety and tolerance [ Time Frame: 2 cycles of Dovitinib application (2 months) ]The primary endpoint is safety and tolerance and will be based on the frequency of DLTs.
- Tumor response (CR, PR) [ Time Frame: 14 months ]Tumor response (CR, PR) according RANO criteria
- Overall safety [ Time Frame: 14 months ]Overall safety
- Disease Control Rate (CR + PR + SD) [ Time Frame: 14 months ]Disease Control Rate (CR + PR + SD)
- Progression free survival rate [ Time Frame: 14 months ]Progression free survival rate at 6 months (PFS-6) and overall survival after initiation of therapy
- Quality of life [ Time Frame: 14 months ]Quality of life (health questionnaires)
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01972750
|Department of Neurology and Center of Integrated Oncology, University Hospital Bonn|
|Bonn, Germany, 53105|
|Principal Investigator:||Martin Glas, MD||Neurooncology, University Hospital Bonn|