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

18 Years
Not Enrolling
Neoplastic Meningitis

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Trial Information

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

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

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

- 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

- 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

- Any condition that impairs patient's ability to swallow whole pills.

- Any malabsorption problem.

- Patients who are pregnant or breast-feeding.

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants With Adverse Events (AEs)

Outcome Description:

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.

Outcome Time Frame:

6 Months

Safety Issue:


Principal Investigator

Edward Pan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

February 2011

Related Keywords:

  • Neoplastic Meningitis
  • Neurologic Oncology
  • Neoplastic Meningitis from solid tumors
  • Brain and Nervous System
  • Breast Cancer
  • Meningitis
  • Meningeal Carcinomatosis



H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612