Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis

NCT01373710 | Completed Phase 1 DMC

• 2 other identifiers: 09/501/M2009-017218-63
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 10

Brief 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

Conditions

Metastatic Breast Cancer; Carcinomatous Meningitis

Keywords

Adverse Reaction to Trastuzumab Administered by intrathecal

Outcome Measures

Primary Outcomes (1)

• 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).

  2 months

Secondary Outcomes (10)

• Phase I : Recommended dose (RD will be used in Phase II)

  2 months

• Phase I&II : Toxicity during treatment

  2 months

• Time to neurologic progression

  2 years

• Biological response: CSF cellularity and protein concentration

  2 years

• Radiological response: cerebrospinal meningitis and neuraxis MRI

  2 years

Study Arms (1)

Trastuzumab intrathecal

EXPERIMENTAL

Drug: Trastuzumab

Interventions

Trastuzumab 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

Also known as: Herceptin

Trastuzumab intrathecal

Eligibility Criteria

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

You may qualify if:

• Metaplastic Infiltrating adenocarcinoma of the breast
• HER2 Overexpression by IHC and / or amplification (FISH and or ICHS)
• 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
• Women of childbearing potential, must take adequate birth control measure during the study period and must have a negative pregnancy test (BetaHCG serum)
• Signed written inform consent

You may not qualify if:

• 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)

Sponsors & Collaborators

• Institut Curie: lead
• Hoffmann-La Roche: collaborator
• Centre Leon Berard: collaborator
• Groupe Hospitalier Pitie-Salpetriere: collaborator
• Centre Oscar Lambret: collaborator
• Centre Francois Baclesse: collaborator
• Institut Bergonié: collaborator
• University Hospital, Toulouse: collaborator
• Institut du Cancer de Montpellier - Val d'Aurelle: collaborator
• University Hospital, Grenoble: collaborator

Study Sites (10)

François Baclesse Center

Caen, Calvados, 14076, France

Location

Rene Huguenin Hospital

Saint-Cloud, Haut de Seine, 92210, France

Location

Oscar Lambret Center

Lille, Nord, 59020, France

Location

Léon Bérard Center

Lyon, Rhone, 69373, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

CHU Grenoble

Grenoble, 38700, France

Location

Institut du Cancer de Montpellier

Montpellier, 34298, France

Location

Institut Univesitaire du Cancer de Toulouse

Toulouse, 31100, France

Location

Institut Curie - Claudius Regaud Hospital

Paris, Île-de-France Region, 75248, France

Location

Pitie Salpetriere Hospital

Paris, Île-de-France Region, 75651, France

Location

Related Publications (1)

• 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.

  PMID: 29635147 RESULT

MeSH Terms

Conditions

Breast Neoplasms; Meningeal Carcinomatosis

Interventions

Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Maya Gutierrez, MD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2011
• First Posted: June 15, 2011
• Study Start: May 19, 2011
• Primary Completion: April 1, 2018
• Study Completion: April 9, 2018
• Last Updated: November 24, 2025

Record last verified: 2025-11

Locations

FR (10)