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Metastatic Breast CancerPhase 1/2HITNCT01373710

Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis

A Phase 1/2 study testing Trastuzumab in people with Metastatic Breast Cancer and Carcinomatous Meningitis, run by Institut Curie at 10 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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)… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Trastuzumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
34 participants
Where
10 sitesFrance
Study dates
19 May 2011to 9 Apr 2018
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

France10 sites

  • Institut Bergonié

    Bordeaux, 33076

  • François Baclesse Center

    Caen, Calvados, 14076

  • CHU Grenoble

    Grenoble, 38700

  • Oscar Lambret Center

    Lille, Nord, 59020

  • Léon Bérard Center

    Lyon, Rhone, 69373

  • Institut du Cancer de Montpellier

    Montpellier, 34298

  • Institut Curie - Claudius Regaud Hospital

    Paris, Île-de-France Region, 75248

  • Pitie Salpetriere Hospital

    Paris, Île-de-France Region, 75651

  • Rene Huguenin Hospital

    Saint-Cloud, Haut de Seine, 92210

  • Institut Univesitaire du Cancer de Toulouse

    Toulouse, 31100

Other trials in France

About this study

Official title: Phase 1-2 Study of Safety and Efficacy of Intrathecal Trastuzumab Administration in Metastatic HER2 Positive Breast Cancer Patients Developing Carcinomatous Meningitis

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

Read the 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

Being tested
Trastuzumab
Keywords
Adverse Reaction to Trastuzumab Administered by intrathecal
Medical subject headings
Breast Neoplasms, Meningeal Carcinomatosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrastuzumabDrug

    Also called Herceptin

    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

Study groups in NCT01373710
Study groupRoleWhat they receive
Trastuzumab intrathecalExperimentalNot described
Receives: Drug: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 2 months

Secondary outcomes (10)

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

    Measured: 2 months

  2. Phase I&II : Toxicity during treatment

    Issued the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 National Cancer Institute (NCI)

    Measured: 2 months

  3. Time to neurologic progression

    Measured: 2 years

  4. Biological response: CSF cellularity and protein concentration

    Measured: 2 years

  5. Radiological response: cerebrospinal meningitis and neuraxis MRI

    Measured: 2 years

  6. Impact on quality of life

    Measured: 2 years

  7. Impact on survival (overall survival, survival without neurological progression, progression-free survival)

    Measured: 2 years

  8. Pharmacokinetics: dose of trastuzumab in CSF and plasma

    Measured: 2 months

  9. FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer

    Measured: 2 years

  10. Phase II : Determination of antitumor activity trastuzumab when administrated by IT or intra-ventricular in terms of neurological progression free survival at 2 months

    Measured: 2 month

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Jun 2011 (estimated)
  2. Study start19 May 2011
  3. Primary completionApr 2018
  4. Study completion9 Apr 2018

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
34 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01373710
Sponsor's protocol ID
09/501/M
Other IDs
2009-017218-63, 2009
Acronym
HIT
Status last verified
Nov 2025
First submitted
24 May 2011
Last updated
24 Nov 2025
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29635147

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trastuzumab in people with Metastatic Breast Cancer and Carcinomatous Meningitis, run by Institut Curie at 10 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I : To determine the Trastuzumab maximum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route. (time frame: 2 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01373710, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2025.

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