Depocyt® With Sorafenib in Neoplastic Meningitis

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00964743
• Date of registration: 24/08/2009
• Primary sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Public title: Depocyt® With Sorafenib in Neoplastic Meningitis
• Scientific title: A Single Arm Pilot Study of Intrathecally Administered DepoCyt® With Systemic Sorafenib in the Treatment of Neoplastic Meningitis From Solid Tumors
• Date of first enrolment: August 2009
• Target sample size: 2
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT00964743
• Study type: Interventional
• Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Countries of recruitment

United States

Contacts

• Name: Edward Pan, M.D.
• Affiliation: H. Lee Moffitt Cancer Center and Research Institute

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Neoplastic Meningitis

Intervention(s)

Drug: DepoCyt

Drug: Sorafenib

Primary Outcome(s)

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

Secondary Outcome(s)

CSF and Serum Vascular Endothelial Growth Factor (VEGF) Levels [Time Frame: 6 Months]

Number of Participants With Overall Survival (OS) [Time Frame: 6 Months]

Number of Participants With Progression Free Survival (PFS) at 6 Months [Time Frame: 6 Months]

Sorafenib Levels in Cerebrospinal Fluid (CSF) [Time Frame: 6 Months]

Secondary ID(s)

Bayer IST000266

MCC-15783

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Bayer