Depocyt® With Sorafenib in Neoplastic Meningitis

NCT00964743 | Terminated Results DMC

• 2 other identifiers: MCC-15783Bayer IST000266
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Neoplastic Meningitis

Keywords

Neurologic Oncology; Neoplastic Meningitis from solid tumors; Brain and Nervous System; Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Number of Participants With Progression Free Survival (PFS) at 6 Months

  6 Months

• Number of Participants With Overall Survival (OS)

  6 Months

• Sorafenib Levels in Cerebrospinal Fluid (CSF)

  6 Months

• CSF and Serum Vascular Endothelial Growth Factor (VEGF) Levels

  6 Months

Study Arms (1)

Intrathecal DepoCyt and Oral Sorafenib

EXPERIMENTAL

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; Drug: Sorafenib

Interventions

DepoCyt DRUG

Patients were to receive DepoCyt through a reservoir every 2 weeks for 5 doses, then every 4 weeks for an additional 5 doses.

Also known as: Liposomal Cytarabine, cytarabine liposome injection

Intrathecal DepoCyt and Oral Sorafenib

Sorafenib DRUG

Patients received oral sorafenib at 400 mg twice a day

Also known as: Nexavar, BAY 43-9006, oral multi-kinase inhibitor

Intrathecal DepoCyt and Oral Sorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bayer: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Meningeal Carcinomatosis; Neurologic Manifestations; Breast Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Meningeal Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

The study closed early due to low accrual of 2 of 10 expected patients. Neither patient completed 8 weeks of treatment as outlined in the protocol. Both patients expired before reaching the 6 month Progression Free Survival endpoint.

Results Point of Contact

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

edward.pan@moffitt.org

813-745-3871

Study Officials

• Edward Pan, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2009
• First Posted: August 25, 2009
• Study Start: August 1, 2009
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: September 9, 2013
• Results First Posted: April 19, 2012

Record last verified: 2012-01

Locations

US (1)