Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis (HIT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2011 by Institut Curie
Sponsor:
Collaborators:
Hoffmann-La Roche
Gustave Roussy, Cancer Campus, Grand Paris
Centre Leon Berard
Groupe Hospitalier Pitie-Salpetriere
Centre Oscar Lambret
Centre Francois Baclesse
Institut Bergonié
ICO Paul Papin
Information provided by (Responsible Party):
Institut Curie
ClinicalTrials.gov Identifier:
NCT01373710
First received: May 24, 2011
Last updated: January 6, 2014
Last verified: June 2011

May 24, 2011
January 6, 2014
May 2011
May 2015   (final data collection date for 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 ] [ Designated as safety issue: Yes ]
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).
Same as current
Complete list of historical versions of study NCT01373710 on ClinicalTrials.gov Archive Site
  • Phase I : Recommended dose (RD will be used in Phase II) [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • Phase I&II : Toxicity during treatment [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Issued the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 National Cancer Institute (NCI)
  • Time to neurologic progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Biological response: CSF cellularity and protein concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Radiological response: cerebrospinal meningitis and neuraxis MRI [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Impact on quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Impact on survival (overall survival, survival without neurological progression, progression-free survival) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: dose of trastuzumab in CSF and plasma [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Phase I : Recommended dose (RD will be used in Phase II) [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • Phase I&II : Toxicity during treatment [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
    Issued the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 National Cancer Institute (NCI)
  • Time to neurologic progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Biological response: CSF cellularity and protein concentration [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Radiological response: cerebrospinal meningitis and neuraxis RMI [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Impact on quality of life [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Impact on survival (overall survival, survival without neurological progression, progression-free survival) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Pharmacokinetics: dose of trastuzumab in CSF and plasma [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis
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

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

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Metastatic Breast Cancer
  • Carcinomatous Meningitis
Drug: 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
Other Name: Herceptin
Experimental: Trastuzumab intrathecal
Intervention: Drug: Trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
37
May 2017
May 2015   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact: Emmanuelle Fourme, MD +33 1 47 11 16 59 emmanuelle.fourme@curie.net
Contact: Isabelle Turbiez, CRA + 33 11 47 11 16 59 isabelle.turbiez@curie.net
France
 
NCT01373710
09/501/M, 2009-017218-63
Yes
Institut Curie
Institut Curie
  • Hoffmann-La Roche
  • Gustave Roussy, Cancer Campus, Grand Paris
  • Centre Leon Berard
  • Groupe Hospitalier Pitie-Salpetriere
  • Centre Oscar Lambret
  • Centre Francois Baclesse
  • Institut Bergonié
  • ICO Paul Papin
Study Director: Maya Gutierrez, MD Institut Curie - Hopital Rene Huguenin - Saint-Cloud - France
Institut Curie
June 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP