Clinical trial · Interventional
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
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (2)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Carcinomatous Meningitis | Meningeal Carcinomatosis | ALIAS | 0.90 |
| Metastatic Breast Cancer | Malignant Breast Neoplasm | CURATED_BROADER | 0.78 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Trastuzumab | Drug | Trastuzumab | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Trastuzumab intrathecal
- interventionNames
- Drug: Trastuzumab
Primary outcomes (1)
- measure
- Phase I : To determine the Trastuzumab maximum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route.
- timeFrame
- 2 months
- description
- 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 outcomes (10)
- measure
- Phase I : Recommended dose (RD will be used in Phase II)
- timeFrame
- 2 months
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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)
References
Publications (1)
- RESULTBonneau 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