Clinical Trial: Depocyt® With Sorafenib in Neoplastic Meningitis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: A Single Arm Pilot Study of Intrathecally Administered DepoCyt® With Systemic Sorafenib in the Treatment of Neoplastic Meningitis From Solid Tumors

Brief Summary: The purpose of this study is to determine the tolerability and side effects of oral sorafenib in combination with intrathecal DepoCyt.

Detailed Summary: After an Ommaya reservoir has been placed in the patient's head, the patient will receive DepoCyt through that reservoir every 2 weeks for 5 doses, then every 4 weeks for an additional 5 doses (a total of 10 DepoCyt treatments). Patients will also receive oral sorafenib at 400 mg twice a day throughout the treatment course until disease progression or death. Patients will receive brain magnetic resonance imaging (MRIs) with contrast (and whole spine, if necessary) and spinal fluid studies will be obtained every 8 weeks through the Ommaya reservoir until disease progression, death, or unacceptable toxicity. In addition, patients will have spinal fluid obtained to test for sorafenib levels at each study visit after the start of sorafenib as well as prior to sorafenib treatment for controls.
Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Current Primary Outcome: Number of Participants With Adverse Events (AEs) [ Time Frame: 6 Months ]

Safety and tolerability of sorafenib with DepoCyt. Toxicities were to be reported using tables and descriptive statistics by type and grade. All patients were to be followed up until death.


Original Primary Outcome: Safety and Tolerability. Toxicities will be reported using tables and descriptive statistics by type and grade. [ Time Frame: 6 Months. All patients will be followed up until death. ]

Current Secondary Outcome:

  • Number of Participants With Progression Free Survival (PFS) at 6 Months [ Time Frame: 6 Months ]
    Kaplan-Meier analysis of PFS was to be performed and the PFS at 6 months in the study patients were be empirically described. All patients were to be followed up until death.
  • Number of Participants With Overall Survival (OS) [ Time Frame: 6 Months ]
    Several secondary endpoints were to be analyzed in a descriptive fashion. All patients were to be followed up until death.
  • Sorafenib Levels in Cerebrospinal Fluid (CSF) [ Time Frame: 6 Months ]
    CSF sorafenib level was to be measured over time, and the means and standard errors of the sorafenib level were to be plotted at specific sampling time points. CSF sorafenib levels may also have been correlated with patients' PFS, OS, or cytology using descriptive statistical methods (e.g., KM analysis stratified by high vs. low CSF sorafenib levels). The log transformation of lab values were to be employed on the continuous variables whenever necessary.
  • CSF and Serum Vascular Endothelial Growth Factor (VEGF) Levels [ Time Frame: 6 Months ]
    CSF and serum VEGF levels were to be measured over time, and the means and standard errors of the respective VEGF levels were to be plotted at specific sampling time points. The respective VEGF levels may also have been correlated with patients' PFS, OS, or cytology using descriptive statistical methods similarly as mentioned above. The log transformation of lab values were to be employed on the continuous variables whenever necessary.


Original Secondary Outcome:

  • Estimate the Progression Free Survival (PFS) at 6 months. Kaplan-Meier analysis of PFS will be performed and the PFS at 6 months in the study patients will be empirically described. [ Time Frame: 6 Months. All patients will be followed up until death. ]
  • Overall Survival. Several secondary endpoints will be analyzed in a descriptive fashion. [ Time Frame: 6 Months. All patients will be followed up until death. ]
  • Evaluate cytological response to treatment with Sorafenib. [ Time Frame: 6 Months. All patients will be followed up until death. ]
  • Determine the presence of Sorafenib in CSF. [ Time Frame: 6 Months. All patients will be followed up until death. ]
  • Determine the concentration of VEGF in CSF in study patients [ Time Frame: 6 Months. All patients will be followed up until death. ]
  • Correlate CSF VEGF concentration with (a)CSF sorafenib concentration, (b) serum VEGF concentration, and (c) patient outcome. [ Time Frame: 6 Months. All patients will be followed up until death. ]


Information By: H. Lee Moffitt Cancer Center and Research Institute

Dates:
Date Received: August 24, 2009
Date Started: August 2009
Date Completion:
Last Updated: September 4, 2013
Last Verified: January 2012