| Study 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 400mg twice a day throughout the treatment course until disease progression or
death. Patients will receive brain 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. |
| Criteria: |
|
Inclusion Criteria:
- Patients must have neoplastic meningitis from solid tumor malignancy (excluding
metastatic melanoma, leukemia, lymphoma, or primary malignant glioma) diagnosed by:
Positive CSF cytology - OR - Definitive neurologic signs/symptoms of NM with positive
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 ULN, ALT and AST ≤ 2.5 times the ULN ( ≤ 5 x
ULN for patients with liver involvement), Creatinine ≤ 1.5 times ULN, INR < 1.5 or a
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 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:
- 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 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
CSF flow blockage that is subsequently proven to be relieved after focal 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 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 > 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. |