Prospective controlled phase 2 trial of cabazitaxel in patients with temozolomide refractory glioblastoma multiforme (GBM)- The C-GBM Study

Phase 1

Active, not recruiting

Conditions: •Patients with diagnosis glioblastoma multiforme (GBM) WHO grade IV
•Progression during or within 6 months after last temozolomide treatment
•Time since last temozolomide > 21 days
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2013-001550-98-DE

Lead Sponsor: niversity Hospital of Ulm

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Not Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

· 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 33
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 13

Exclusion Criteria

· Female patients who are pregnant or breast-feeding
· History of severe hypersensitivity reaction (=grade 3) to any component of the investigational drugs or excipients (allergy to or other intolerability of gadolinium, docetaxel, cabazitaxel or polysorbate 80 containing drugs)
· Unable to undergo Gd-MRI
· Time since external beam radiotherapy <12 weeks
· Patients who have been treated with any investigational agent(s) within 28 days of the first day of administration of study drug.
· Current active second malignancy other than non-melanoma skin cancers and post-treatment of localized prostate cancer. Patients are not considered to have a currently active malignancy if they are in complete remission for > 3 years prior to study
· Uncontrolled severe illness or medical condition (including uncontrolled diabetes mellitus)
· Known HIV infection, active Hepatitis B or C infection
· Any serious and/or unstable pre-existing psychiatric or other condition that could interfere with subject’s safety, provision of informed consent, or compliance to study procedures
· Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity (except alopecia) and delayed hematological recovery following last temozolomide cycle
· Additional anti-cancer treatment for GBM other than study drug and supportive measures (i.e. dexamethason)
· Inadequate organ and bone marrow function as evidenced by:
a) Hemoglobin <9.0 g/dL
b) Absolute neutrophil count <1.5 x 109/L,
c) Platelet count <100 x 109/L,
d) AST/SGOT and/or ALT/SGPT >2.5 x ULN;
e) Total bilirubin >1.0 x ULN,
f) Serum creatinine >1.5 x ULN.
If creatinine 1.0 - 1.5 x ULN, creatinine clearance will be calculated
according to CKD-EPI formula and patients with creatinine clearance <60 mL/min should be excluded

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Primary Objective<br>• Response after 12 weeks;Secondary Objective: Secondary Objectives<br>• Impact on progression and overall survival<br>• Pharmacokinetics of cabazitaxel in patients with and without concomitant anticonvulsive medication with respect to induction of CYP3A<br>• 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.;Primary end point(s): • Response including SD, PR or CR determined by MRI (modified RANO criteria);Timepoint(s) of evaluation of this end point: The response to treatment will be evaluated continuously after every two treatment cycles (in 42 day intervals) using the response criteria defined by the Response Assessment in Neuro-Oncoloy Working Group (RANO, Wen et al., 2010; Appendix<br>III).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Primary Endpoint<br>· Overall and progression-free survival<br>· Safety and tolerability<br>· Pharmacokinetics data concerning drug interactions (i.e. CYP3A<br>induction)<br>· Quality of life and neurocognitive functioning<br><br>Safety endpoints<br>· Rates of deaths within 12 weeks<br>· Hematological and non hematological toxicity grade = 2 according to CTCAE V4.0;Timepoint(s) of evaluation of this end point: A first safety assessment will be performed after treatment of 12 patients. Safety assessment will be based on an observation period of each patient of at least four cycles (12 weeks).