Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis
Information source: Institut Curie
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metastatic Breast Cancer; Carcinomatous Meningitis
Intervention: Trastuzumab (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: Institut Curie Official(s) and/or principal investigator(s): Maya Gutierrez, MD, Study Director, Affiliation: Institut Curie - Hopital Rene Huguenin - Saint-Cloud - France
Overall contact: Emmanuelle Fourme, MD, Phone: +33 1 47 11 16 59, Email: emmanuelle.fourme@curie.net
Summary
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
Clinical Details
Official title: Phase 1-2 Study of Safety and Efficacy of Intrathecal Trastuzumab Administration in Metastatic HER2 Positive Breast Cancer Patients Developing Carcinomatous Meningitis
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Phase I : To determine the Trastuzumab maximum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route.
Secondary outcome: Phase I : Recommended dose (RD will be used in Phase II)Phase I&II : Toxicity during treatment 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 FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer Phase II : Determination of antitumor activity trastuzumab when administrated by IT or intra-ventricular in terms of neurological progression free survival at 2 months
Detailed description:
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
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Metaplastic Infiltrating adenocarcinoma of the breast
- HER2 Overexpression by IHC and / or amplification (FISH and or ICHS)
- Positive diagnosis of neoplastic meningitis: positive CSF cytology (obtained within
28 days before inclusion) AND / OR clinical symptoms of neoplastic meningitis and
aspect of tumoral meningitis on MRI
- Brain metastases are allowed without prior treatment, if they are asymptomatics and
without engagement. In cases of symptomatic brain metastases, subjects could be
included only if surgery and / or radiotherapy (stereotactic or in toto) were
performed and if the cerebral metastatic localization allow IT or intra-ventricular
treatment. The last radiotherapy session or the surgery must have been done 3 weeks
before.
- Aged 18 years old or more
- Male and female
- Life expectancy more than 2 months
- Satisfactory Cardiac function: left ventricular ejection fraction (LVEF) determined
by ultrasound scan or myocardial scintigraphy
- Adequate Biological functions 14 days before inclusion, according to the criteria
below: Neutrophils > 1. 0 x 109/L, Hemoglobin > 9. 0 g/dL (+ transfusion if
needed,Platelets > 50 x 109/L,Bilirubin < 3 x N, ALT & AST < 10 x N, Creatinine < 2. 0
mg/dL, Clearance > 25 mL/min (Cockcroft and Gault formula), Prothrombin time > 70 %,
Kaolin cephalin coagulation time < 1. 5 x N.
- Women of childbearing potential, must take adequate birth control measure during the
study period and must have a negative pregnancy test (BetaHCG serum)
- The subjects must perform all evaluations of pre-inclusion, as provided by the
protocol
- Signed written inform consent
Exclusion Criteria:
- CSF circulation disorders suspected on MRI brain (obstructive hydrocephalus) or
medullar (obstacle) with, in case of a focal radiotherapy on obstructive lesion,
checking the restoration of transit traffic by isotope CSF
- Anti-coagulant effective dose treatment when trastuzumab administration by lumbar
puncture
- Patient on Lapatinib (wash out> 2 weeks from the date of first dose intrathecal
trastuzumab)
- Known or suspected trastuzumab allergy
- Contraindications of trastuzumab administration, including cardiac diseases: LVEF
- Severe toxicity unresolved or unstable related to another previous study restricted
drug and / or a cancer treatment
- Ventriculoperitoneal or atrial shunting excepted if the valve could be turn off
(on-off switch) and the patient can stand it during 6 h after each injection of
trastuzumab
- Dementia, altered mental status or psychiatric condition that would prevent the
subject to understand or give informed consent
- Pre-existing severe cerebrovascular disease, such as stroke in a major vessel,
vasculitis in the central nervous system or malignant hypertension
- Uncontrolled infection
- Participation in a clinical study with an experimental molecule
- No affiliation to a Social insurance (beneficiary or assignee)
- Pregnant women, breastfeeding or of childbearing age not taking contraceptive
- Subject unable to make follow up schedule
- Persons deprived of liberty or under guardianship (including curators)
Locations and Contacts
Emmanuelle Fourme, MD, Phone: +33 1 47 11 16 59, Email: emmanuelle.fourme@curie.net
François Baclesse Center, Caen, Calvados 14076, France; Recruiting Gunzer Katharina, MD, Phone: +33231455002, Email: k.gunzer@baclesse.fr Gunzer Katharina, MD, Principal Investigator
Rene Huguenin Hospital, Saint-Cloud, Haut de Seine 92210, France; Recruiting Maya Gutierrez, MD, Phone: +33147111515, Email: maya.gutierrez@curie.net Maya Gutierrez, MD, Principal Investigator
Institut Curie - Claudius Regaud Hospital, Paris, Ile de France 75248, France; Recruiting DIERAS Veronique, MD, Phone: +33144324675, Email: veronique.dieras@curie.net Dieras Veronique, MD, Principal Investigator
Pitie Salpetriere Hospital, Paris, Ile de France 75651, France; Recruiting Taillibert Sophie, MD, Phone: +33142160385, Email: sophie.taillibert@psl.aphp.fr Taillibert Sophie, MD, Principal Investigator
Oscar Lambret Center, Lille, Nord 59020, France; Recruiting Le Rhun Emilie, MD, Phone: +33320295935, Email: e-lerhun@o-lambret.fr Le Rhun Emilie, MD, Principal Investigator
Léon Bérard Center, Lyon, Rhone 69373, France; Recruiting Tredan Olivier, MD, Phone: +33478782644, Email: tredan@lyon.fnclcc.fr
Additional Information
Starting date: May 2011
Last updated: September 5, 2014
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