Depocyt® With Sorafenib in Neoplastic Meningitis

This study has been terminated.
(Low Accrual)
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00964743
First received: August 24, 2009
Last updated: September 4, 2013
Last verified: January 2012
  Purpose

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


Condition Intervention
Neoplastic Meningitis
Drug: DepoCyt
Drug: Sorafenib

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm Pilot Study of Intrathecally Administered DepoCyt® With Systemic Sorafenib in the Treatment of Neoplastic Meningitis From Solid Tumors

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Adverse Events (AEs) [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Number of Participants With Progression Free Survival (PFS) at 6 Months [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Enrollment: 2
Study Start Date: August 2009
Study Completion Date: February 2011
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intrathecal DepoCyt and Oral Sorafenib
This is a single arm pilot study. Investigators planned to enroll approximately 10 patients to receive concurrent intrathecal DepoCyt and oral Sorafenib. DepoCyt: through a reservoir every 2 weeks for 5 doses, then every 4 weeks for an additional 5 doses (a total of 10 DepoCyt treatments). Oral Sorafenib: at 400 mg twice a day throughout the treatment course until disease progression or death.
Drug: DepoCyt
Patients were to receive DepoCyt through a reservoir every 2 weeks for 5 doses, then every 4 weeks for an additional 5 doses.
Other Names:
  • Liposomal Cytarabine
  • cytarabine liposome injection
Drug: Sorafenib
Patients received oral sorafenib at 400 mg twice a day
Other Names:
  • Nexavar
  • BAY 43-9006
  • oral multi-kinase inhibitor

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have neoplastic meningitis (NM) from solid tumor malignancy (excluding metastatic melanoma, leukemia, lymphoma, or primary malignant glioma) diagnosed by: Positive cerebrospinal fluid (CSF) cytology - or - Definitive neurologic signs/symptoms of NM with positive magnetic resonance imaging (MRI) findings or supportive CSF profile.
  • Adequate bone marrow, liver, and renal function as assessed by the following: Hemoglobin ≥ 9.0 g/dl, Absolute neutrophil count (ANC) ≥ 1,500/mm³, Platelet count ≥ 100,000/mm³, Total bilirubin ≤ 1.5 times upper limit of normal (ULN), alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 times the ULN ( ≤ 5 x ULN for patients with liver involvement), Creatinine ≤ 1.5 times ULN, international normalized ratio (INR) < 1.5 or a prothrombin time/partial thromboplastin time (PT/PTT) within normal limits. Patients receiving anti-coagulation treatment with an agent such as warfarin or heparin may be allowed to participate. For patients on warfarin, the international normalized ratio (INR) should be measured prior to initiation of sorafenib and monitored at least weekly, or as defined by the local standard of care, until INR is stable
  • Must have a Karnofsky performance score ≥ 60% (i.e. the patient must be able to care for himself/herself with occasional help from others)
  • Must be healthy enough to receive ventricular access device (VAD) placement.
  • Patients with a ventriculoperitoneal (VP) shunt that have an on/off device in their shunt systems are eligible for the study provided they are able to tolerate shunt closure for ≥ 4 hours without developing clinical signs of increased intracranial pressure.
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test performed within 7 days prior to the start of treatment
  • WOCBP and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation. Men should use adequate birth control for at least 3 months after the last administration of sorafenib.
  • Ability to understand and the willingness to sign a written informed consent. A signed informed consent must be obtained prior to any study specific procedures.

Exclusion Criteria:

  • Neoplastic meningitis (NM) from metastatic melanoma, leukemia, lymphoma, or primary malignant glioma
  • Uncontrolled systemic disease from their primary cancer
  • Must not have had prior intrathecal chemotherapy, sorafenib, or brain or spine radiation for the treatment of neoplastic meningitis.
  • Concomitant therapy with high-dose systemic methotrexate, cytarabine, thiotepa, or an agent known to have penetration into the central nervous system (CNS)
  • Patients with clinical evidence of obstructive hydrocephalus or compartmentalization of CSF flow as documented by radioisotope Indium (Technetium-DTPA when Indium unavailable) flow study are not eligible for this trial. If patients have evidence of cerebrospinal fluid (CSF) flow blockage that is subsequently proven to be relieved after focal radiation therapy (XRT), they can enroll immediately after repeat flow study shows block to be relieved.
  • Use of any investigational drug within 28 days prior to study entry.
  • Patients with a life expectancy of ≤ 2 months
  • Cardiac disease: Congestive heart failure > class II New York Heart Association (NYHA). Must not have unstable angina or new onset angina (began within the last 3 months)or myocardial infarction within past 6 months.
  • Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
  • Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
  • Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
  • Active clinically serious infection > Common Terminology Criteria for Adverse Events (CTCAE) Grade 2.
  • Thrombolic or embolic events such as a cerebrovascular accident including transient ischemic attacks within past 6 months.
  • Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug.
  • Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug.
  • Serious non-healing wound, ulcer, or bone fracture.
  • Evidence or history of bleeding diathesis or coagulopathy
  • Major surgery, open biopsy or significant traumatic injury within 4 weeks of first study drug.
  • Use of St. John's Wort or rifampin.
  • Known or suspected allergy to sorafenib or any agent given in the course of this trial.
  • Any condition that impairs patient's ability to swallow whole pills.
  • Any malabsorption problem.
  • Patients who are pregnant or breast-feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00964743

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bayer
Investigators
Principal Investigator: Edward Pan, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT00964743     History of Changes
Other Study ID Numbers: MCC-15783, Bayer IST000266
Study First Received: August 24, 2009
Results First Received: January 19, 2012
Last Updated: September 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Neurologic Oncology
Neoplastic Meningitis from solid tumors
Brain and Nervous System
Breast Cancer

Additional relevant MeSH terms:
Meningitis
Meningeal Carcinomatosis
Central Nervous System Infections
Central Nervous System Diseases
Nervous System Diseases
Meningeal Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Neoplasms
Cytarabine
Sorafenib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 26, 2014