Depocyt® With Sorafenib in Neoplastic Meningitis

Neoplastic Meningitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00964743
• Other study ID #: MCC-15783
• Secondary ID: Bayer IST000266
• Status: Terminated
• Phase: N/A
• First received: August 24, 2009
• Last updated: September 4, 2013
• Start date: August 2009
• Est. completion date: February 2011

Study information

• Verified date: January 2012
• Source: H. Lee Moffitt Cancer Center and Research Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2011
• Est. primary completion date: February 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Meningeal Carcinomatosis
• Meningitis
• Neoplastic Meningitis

Intervention

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.
• Sorafenib
Patients received oral sorafenib at 400 mg twice a day

Locations

Country	Name	City	State
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
H. Lee Moffitt Cancer Center and Research Institute	Bayer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Adverse Events (AEs)	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.	6 Months	Yes
Secondary	Number of Participants With Progression Free Survival (PFS) at 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.	6 Months	No
Secondary	Number of Participants With Overall Survival (OS)	Several secondary endpoints were to be analyzed in a descriptive fashion. All patients were to be followed up until death.	6 Months	No
Secondary	Sorafenib Levels in Cerebrospinal Fluid (CSF)	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.	6 Months	No
Secondary	CSF and Serum Vascular Endothelial Growth Factor (VEGF) Levels	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.	6 Months	No

External Links

•   Moffitt Cancer Center Clinical Trials website