Clinical Trial: Intrathecal Trastuzumab Administration in Metastatic Breast Cancer Patients Developing Carcinomatous Meningitis
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Phase 1-2 Study of Safety and Efficacy of Intrathecal Trastuzumab Administration in Metastatic HER2 Positive Breast Cancer Patients Developing Carcinomatous Meningitis
Brief 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)
Phase II: Determination of antitumor activity trastuzumab when administrated by IT or intra-ventricular in terms of neurological progression-free survival at 2 months
Detailed Summary:
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
Sponsor: Institut Curie
Current Primary Outcome: Phase I : To determine the Trastuzumab maximum tolerated dose (MTD) when weekly administrated by intrathecal or intraventricular route. [ Time Frame: 2 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Phase I : Recommended dose (RD will be used in Phase II) [ Time Frame: 2 months ]
- Phase I&II : Toxicity during treatment [ Time Frame: 2 months ]Issued the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 National Cancer Institute (NCI)
- Time to neurologic progression [ Time Frame: 2 years ]
- Biological response: CSF cellularity and protein concentration [ Time Frame: 2 years ]
- Radiological response: cerebrospinal meningitis and neuraxis MRI [ Time Frame: 2 years ]
- Impact on quality of life [ Time Frame: 2 years ]
- Impact on survival (overall survival, survival without neurological progression, progression-free survival) [ Time Frame: 2 years ]
- Pharmacokinetics: dose of trastuzumab in CSF and plasma [ Time Frame: 2 months ]
- FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer [ Time Frame: 2 years ]
- 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 ]
Original Secondary Outcome:
- Phase I : Recommended dose (RD will be used in Phase II) [ Time Frame: 2 months ]
- Phase I&II : Toxicity during treatment [ Time Frame: 2 months ]Issued the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 National Cancer Institute (NCI)
- Time to neurologic progression [ Time Frame: 2 years ]
- Biological response: CSF cellularity and protein concentration [ Time Frame: 2 years ]
- Radiological response: cerebrospinal meningitis and neuraxis RMI [ Time Frame: 2 years ]
- Impact on quality of life [ Time Frame: 2 years ]
- Impact on survival (overall survival, survival without neurological progression, progression-free survival) [ Time Frame: 2 years ]
- Pharmacokinetics: dose of trastuzumab in CSF and plasma [ Time Frame: 2 months ]
- FCGR3A Genetic status influence on efficacy trastuzumab in metastatic breast cancer [ Time Frame: 2 years ]
- 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 ]
Information By: Institut Curie
Dates:
Date Received: May 24, 2011
Date Started: May 2011
Date Completion: May 2019
Last Updated: January 23, 2017
Last Verified: January 2017