Glioblastoma Multiforme (GBM) WHO Grade IV
Conditions
Brief summary
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.
Interventions
DRUGCabazitaxel
Sponsors
University of Ulm
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Both female and male patients meeting the mentioned inclusion and
Exclusion criteria
will be included in this clinical trial. Patients must meet ALL of the following inclusion criteria to be eligible for enrollment into the study: * Patients with diagnosis glioblastoma multiforme (GBM) WHO grade IV (histologically confirmed by a pathologist) * Progression during or within 6 months after last temozolomide treatment * Time since last temozolomide \> 21 days * Prior external beam radiotherapy (54 to 62 Gy), no option for subsequent radiotherapy * No clinical and radiological signs of intracerebral inflammation (in pre-study MRI not older than 4 weeks) * Patients \> 18 years of age. * ECOG performance status of ≤ 2 (stable over 4 weeks prior to study entrance) * Female patients of childbearing potential with a negative pregnancy test within 7 days of initiation of study treatment. Postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. * Male and female patients of reproductive potential who agree to employ an effective method of birth control throughout the study and for up to 6 months following discontinuation of study drug. * Signed informed consent prior to initiation of any study procedure (Must understand, voluntarily sign the informed consent form and be able to adhere to the study visit schedule and other protocol requirements.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response including SD, PR or CR determined by MRI (modified RANO criteria) | 1 year | • Response after 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality of life and neurocognitive functioning | 3 years | 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 |
| Overall and progression-free survival | 3 years | — |
| Safety and tolerability | 3 years | * Rates of deaths within 12 weeks * Hematological and non hematological toxicity grade ≥ 2 according to CTCAE V4.0 |
| Pharmacokinetics data concerning drug interactions (i.e. CYP3A induction) | 3 years | Pharmacokinetics of cabazitaxel in patients with and without concomitant anticonvulsive medication with respect to induction of CYP3A |
Countries
Germany
Outcome results
None listed