Prospective Phase 2 Trial of Cabazitaxel in Patients With Temozolomide Refractory Glioblastoma Multiforme

NCT01866449 | Completed Phase 2 DMC

• 1 other identifier: C-GBM (XRP6258)
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 3

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.

Conditions

Glioblastoma Multiforme (GBM) WHO Grade IV

Outcome Measures

Primary Outcomes (1)

• Response including SD, PR or CR determined by MRI (modified RANO criteria)

  • Response after 12 weeks

  1 year

Secondary Outcomes (4)

• Overall and progression-free survival

  3 years

• Safety and tolerability

  3 years

• Pharmacokinetics data concerning drug interactions (i.e. CYP3A induction)

  3 years

• Quality of life and neurocognitive functioning

  3 years

Study Arms (1)

Cabazitaxel

EXPERIMENTAL

Cabazitaxel will be given at a dose of 25mg/m² as 1h infusion every 3 weeks

Drug: Cabazitaxel

Interventions

Cabazitaxel DRUG

Also known as: Jevtane

Cabazitaxel

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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.)
• The presence of ANY of the following criteria will exclude a patient from study enrollment:
• 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

Sponsors & Collaborators

• University of Ulm: lead

Study Sites (3)

Hämatologisch onkologische Praxis

Augsburg, 86150, Germany

Location

Stiftungsklinikum Mittelrhein GmbH

Koblenz, 56068, Germany

Location

Lars Bullinger, MD

Ulm, 89081, Germany

Location

MeSH Terms

Conditions

Glioblastoma

Interventions

cabazitaxel

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: May 22, 2013
• First Posted: May 31, 2013
• Study Start: October 1, 2013
• Primary Completion: December 1, 2016
• Study Completion: August 25, 2017
• Last Updated: October 26, 2017

Record last verified: 2017-09

Locations

DE (3)