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 ]

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).


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