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

This is an interventional treatment trial for Metastatic Breast Cancer focused on measuring Adverse Reaction to Trastuzumab Administered by intrathecal Read More

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)