Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis

NCT ID: NCT01373710

Last Updated: 2025-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

34 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-19

Study Completion Date

2018-04-09

Brief Summary

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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

Detailed Description

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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

Conditions

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Metastatic Breast Cancer Carcinomatous Meningitis

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Trastuzumab intrathecal

Group Type EXPERIMENTAL

Trastuzumab

Intervention Type DRUG

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

Interventions

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Trastuzumab

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

Intervention Type DRUG

Other Intervention Names

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Herceptin

Eligibility Criteria

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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 \<laboratory lower limit of normal or any other heart condition which would expose the subject to an unreasonable risk if he were to participate in the study
* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role collaborator

Centre Leon Berard

OTHER

Sponsor Role collaborator

Groupe Hospitalier Pitie-Salpetriere

OTHER

Sponsor Role collaborator

Centre Oscar Lambret

OTHER

Sponsor Role collaborator

Centre Francois Baclesse

OTHER

Sponsor Role collaborator

Institut Bergonié

OTHER

Sponsor Role collaborator

University Hospital, Toulouse

OTHER

Sponsor Role collaborator

Institut du Cancer de Montpellier - Val d'Aurelle

OTHER

Sponsor Role collaborator

University Hospital, Grenoble

OTHER

Sponsor Role collaborator

Institut Curie

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Maya Gutierrez, MD

Role: STUDY_DIRECTOR

Institut Curie - Hopital Rene Huguenin - Saint-Cloud - France

Locations

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François Baclesse Center

Caen, Calvados, France

Site Status

Rene Huguenin Hospital

Saint-Cloud, Haut de Seine, France

Site Status

Oscar Lambret Center

Lille, Nord, France

Site Status

Léon Bérard Center

Lyon, Rhone, France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

CHU Grenoble

Grenoble, , France

Site Status

Institut du Cancer de Montpellier

Montpellier, , France

Site Status

Institut Univesitaire du Cancer de Toulouse

Toulouse, , France

Site Status

Institut Curie - Claudius Regaud Hospital

Paris, Île-de-France Region, France

Site Status

Pitie Salpetriere Hospital

Paris, Île-de-France Region, France

Site Status

Countries

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France

References

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Bonneau C, Paintaud G, Tredan O, Dubot C, Desvignes C, Dieras V, Taillibert S, Tresca P, Turbiez I, Li J, Passot C, Mefti F, Mouret-Fourme E, Le Rhun E, Gutierrez M. Phase I feasibility study for intrathecal administration of trastuzumab in patients with HER2 positive breast carcinomatous meningitis. Eur J Cancer. 2018 May;95:75-84. doi: 10.1016/j.ejca.2018.02.032. Epub 2018 Apr 7.

Reference Type RESULT
PMID: 29635147 (View on PubMed)

Other Identifiers

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2009-017218-63

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

09/501/M

Identifier Type: -

Identifier Source: org_study_id

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