The purpose of this study is: Phase I: To determine the Trastuzumab maximum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route to reach a intra CSF target concentration (30 µg/mL) near the conventional therapeutic concentration and depending on the dose-limiting toxicity (DLT) Phase II: Determination of antitumor activity trastuzumab when administrated by IT or intra-ventricular in terms of neurological progression-free survival at 2 months
Phase I: Secondary Outcome Measures: Recommended dose (RD will be used in Phase II) Toxicity during treatment Clinical response to specific neurologic symptoms Time to neurologic progression Biological response: CSF cellularity and protein concentration Radiological response: cerebrospinal meningitis and neuraxis RMI Impact on quality of life Impact on survival (overall survival, survival without neurological progression, progression-free survival) Pharmacokinetics: dose of trastuzumab in CSF and plasma FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer Phase II: Secondary Outcome Measures : Toxicity during treatment Clinical response to specific neurologic symptoms Time to neurologic progression Biological response: CSF cellularity and protein concentration Radiological response: cerebrospinal meningitis and neuraxis MRI Impact on quality of life Impact on survival (overall survival, survival without neurological progression, progression-free survival) Pharmacokinetics: dose of trastuzumab in CSF and plasma (confirmation of phase I data with 5 patients) FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
34
One injection per week during 8 weeks by lumbar puncture or Ommaya Reservoir. 4 levels of doses are expected from 30 mg to 150 mg
François Baclesse Center
Caen, Calvados, France
Rene Huguenin Hospital
Saint-Cloud, Haut de Seine, France
Oscar Lambret Center
Lille, Nord, France
Léon Bérard Center
Lyon, Rhone, France
Phase I : To determine the Trastuzumab maximum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route.
Phase I : To determine the Trastuzumab maximimum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route to reach a intra CSF target concentration (30 µg/mL) near the conventional therapeutic concentration and depending on the dose-limiting toxicity (DLT).
Time frame: 2 months
Phase I : Recommended dose (RD will be used in Phase II)
Time frame: 2 months
Phase I&II : Toxicity during treatment
Issued the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 National Cancer Institute (NCI)
Time frame: 2 months
Time to neurologic progression
Time frame: 2 years
Biological response: CSF cellularity and protein concentration
Time frame: 2 years
Radiological response: cerebrospinal meningitis and neuraxis MRI
Time frame: 2 years
Impact on quality of life
Time frame: 2 years
Impact on survival (overall survival, survival without neurological progression, progression-free survival)
Time frame: 2 years
Pharmacokinetics: dose of trastuzumab in CSF and plasma
Time frame: 2 months
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Institut Bergonié
Bordeaux, France
CHU Grenoble
Grenoble, France
Institut du Cancer de Montpellier
Montpellier, France
Institut Univesitaire du Cancer de Toulouse
Toulouse, France
Institut Curie - Claudius Regaud Hospital
Paris, Île-de-France Region, France
Pitie Salpetriere Hospital
Paris, Île-de-France Region, France
FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer
Time frame: 2 years
Phase II : Determination of antitumor activity trastuzumab when administrated by IT or intra-ventricular in terms of neurological progression free survival at 2 months
Time frame: 2 month