The proposed study is an open-label, single-arm, Phase- II trial to assess the efficacy of cabazitaxel in GBM WHO grade IV patients with a progression during or within 6 months after last temozolomide treatment (Figure 1). Cabazitaxel will be given at a dose of 25mg/m² as 1h infusion every 3 weeks with standard concomitant medication (as outlined below): * On Day 1 of each cycle, patients will receive cabazitaxel at a dose of 25mg/m², administered by i.v. route in 1 hour. * Cycle length for cabazitaxel is 3 weeks (21 days). * New cycles of therapy may not begin until Absolute Neutrophil Count (ANC) ≥1500/mm3, platelet count ≥75 000/mm3, and non-hematological toxicities (except alopecia) have recovered to baseline. * A maximum of 2 weeks (14 days) delay is allowed between 2 treatment cycles. * Patients should come off treatment if treatment delay is more than 2 weeks. At least 30 minutes prior to each administration of cabazitaxel, patients will receive i.v. premedication including: * An antihistamine (dexchlorpheniramine 5mg, diphenhydramine 25mg, or equivalent). In case of i.v. antihistamine other than promethazine is not being available, local practice should be followed. * Corticosteroid (dexamethasone 8mg or equivalent) * H2 antagonist (ranitidine or equivalent). * Antiemetic prophylaxis is recommended and can be given orally or intravenously if necessary. * Primary prophylaxis with Granulocyte Colony-Stimulating Factor (G-CSF) should be given on day 4 of each treatment cycle as per ASCO and ESMO guidelines.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Hämatologisch onkologische Praxis
Augsburg, Germany
Stiftungsklinikum Mittelrhein GmbH
Koblenz, Germany
Lars Bullinger, MD
Ulm, Germany
Response including SD, PR or CR determined by MRI (modified RANO criteria)
• Response after 12 weeks
Time frame: 1 year
Overall and progression-free survival
Time frame: 3 years
Safety and tolerability
* Rates of deaths within 12 weeks * Hematological and non hematological toxicity grade ≥ 2 according to CTCAE V4.0
Time frame: 3 years
Pharmacokinetics data concerning drug interactions (i.e. CYP3A induction)
Pharmacokinetics of cabazitaxel in patients with and without concomitant anticonvulsive medication with respect to induction of CYP3A
Time frame: 3 years
Quality of life and neurocognitive functioning
Assessment of quality of life, determined by assessment with EORTC QLQ questionnaires (C30 and BN20), and neurocognitive functioning, determined by repeated standardized measurements using MMSE
Time frame: 3 years
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