Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis (HIT)
This study is currently recruiting participants.
Verified June 2011 by Institut Curie
Sponsor:
Institut Curie
Collaborators:
Hoffmann-La Roche
Institut Gustave Roussy
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: April 3, 2012
Last verified: June 2011
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Purpose
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
| Condition | Intervention | Phase |
|---|---|---|
|
Metastatic Breast Cancer Carcinomatous Meningitis |
Drug: Trastuzumab |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase 1-2 Study of Safety and Efficacy of Intrathecal Trastuzumab Administration in Metastatic HER2 Positive Breast Cancer Patients Developing Carcinomatous Meningitis |
Resource links provided by NLM:
Genetics Home Reference related topics:
breast cancer
Drug Information available for:
Trastuzumab
U.S. FDA Resources
Further study details as provided by Institut Curie:
Primary Outcome Measures:
- 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).
Secondary Outcome Measures:
- 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 ]
| Estimated Enrollment: | 37 |
| Study Start Date: | May 2011 |
| Estimated Study Completion Date: | May 2015 |
| Estimated Primary Completion Date: | May 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Trastuzumab intrathecal |
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
|
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| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 <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)
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01373710
Contacts
| 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 |
Locations
| France | |
| François Baclesse Center | Recruiting |
| Caen, Calvados, France, 14076 | |
| Contact: Gunzer Katharina, MD +33231455002 k.gunzer@baclesse.fr | |
| Principal Investigator: Gunzer Katharina, MD | |
| Rene Huguenin Hospital | Recruiting |
| Saint-Cloud, Haut de Seine, France, 92210 | |
| Contact: Maya Gutierrez, MD +33147111515 maya.gutierrez@curie.net | |
| Principal Investigator: Maya Gutierrez, MD | |
| Institut Curie - Claudius Regaud Hospital | Recruiting |
| Paris, Ile de France, France, 75248 | |
| Contact: DIERAS Veronique, MD +33144324675 veronique.dieras@curie.net | |
| Principal Investigator: Dieras Veronique, MD | |
| Pitie Salpetriere Hospital | Recruiting |
| Paris, Ile de France, France, 75651 | |
| Contact: Taillibert Sophie, MD +33142160385 sophie.taillibert@psl.aphp.fr | |
| Principal Investigator: Taillibert Sophie, MD | |
| Oscar Lambret Center | Recruiting |
| Lille, Nord, France, 59020 | |
| Contact: Le Rhun Emilie, MD +33320295935 e-lerhun@o-lambret.fr | |
| Principal Investigator: Le Rhun Emilie, MD | |
| Léon Bérard Center | Recruiting |
| Lyon, Rhone, France, 69373 | |
| Contact: Tredan Olivier, MD +33478782644 tredan@lyon.fnclcc.fr | |
Sponsors and Collaborators
Institut Curie
Hoffmann-La Roche
Institut Gustave Roussy
Centre Leon Berard
Groupe Hospitalier Pitie-Salpetriere
Centre Oscar Lambret
Centre Francois Baclesse
Institut Bergonié
ICO Paul Papin
Investigators
| Study Director: | Maya Gutierrez, MD | Institut Curie - Hopital Rene Huguenin - Saint-Cloud - France |
More Information
No publications provided
| Responsible Party: | Institut Curie |
| ClinicalTrials.gov Identifier: | NCT01373710 History of Changes |
| Other Study ID Numbers: | 09/501/M, 2009-017218-63 |
| Study First Received: | May 24, 2011 |
| Last Updated: | April 3, 2012 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by Institut Curie:
|
Adverse Reaction to Trastuzumab Administered by intrathecal |
Additional relevant MeSH terms:
|
Meningitis Breast Neoplasms Meningeal Carcinomatosis Neoplasms by Site Neoplasms Breast Diseases Skin Diseases Central Nervous System Infections Central Nervous System Diseases |
Nervous System Diseases Meningeal Neoplasms Central Nervous System Neoplasms Nervous System Neoplasms Trastuzumab Antineoplastic Agents Therapeutic Uses Pharmacologic Actions |
ClinicalTrials.gov processed this record on May 23, 2013