Neoplastic MeningitisNCT00964743
Depocyt® With Sorafenib in Neoplastic Meningitis
A study testing DepoCyt and Sorafenib in people with Neoplastic Meningitis, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to determine the tolerability and side effects of oral sorafenib in combination with intrathecal DepoCyt. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplastic Meningitis
- What is being tested?
- DepoCyt and Sorafenib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2009to Feb 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Single Arm Pilot Study of Intrathecally Administered DepoCyt® With Systemic Sorafenib in the Treatment of Neoplastic Meningitis From Solid Tumors
The purpose of this study is to determine the tolerability and side effects of oral sorafenib in combination with intrathecal DepoCyt.
Read the detailed 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.
- Conditions
- Neoplastic Meningitis
- Being tested
- DepoCyt, Sorafenib
- Keywords
- Neurologic Oncology, Neoplastic Meningitis from solid tumors, Brain and Nervous System, Breast Cancer
- Medical subject headings
- Meningeal Carcinomatosis, Neurologic Manifestations, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DepoCytDrug
Also called Liposomal Cytarabine, cytarabine liposome injection
Patients were to receive DepoCyt through a reservoir every 2 weeks for 5 doses, then every 4 weeks for an additional 5 doses.
SorafenibDrug
Also called Nexavar, BAY 43-9006, oral multi-kinase inhibitor
Patients received oral sorafenib at 400 mg twice a day
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: DepoCyt; Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 Months
Secondary outcomes (4)
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.
Measured: 6 Months
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.
Measured: 6 Months
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.
Measured: 6 Months
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.
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Aug 2009 (estimated)
- Study startAug 2009
- Primary completionFeb 2011
- Study completionFeb 2011
Why it stopped: Low Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neoplastic MeningitisStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Edward Pan, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00964743
- Sponsor's protocol ID
- MCC-15783
- Other IDs
- Bayer IST000266
- Status last verified
- Jan 2012
- First submitted
- 24 Aug 2009
- Last updated
- 9 Sep 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm Pilot Study of Intrathecally Administered DepoCyt® With Systemic Sorafenib in the Treatment of Neoplastic Meningitis From Solid Tumors
- ClinicalTrials.gov ID
- NCT00964743
- Acronym / sponsor ID
- MCC-15783
- Conditions
- Neoplastic Meningitis
- Keywords
- Neurologic Oncology, Neoplastic Meningitis from solid tumors, Brain and Nervous System, Breast Cancer
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Aug 2009
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 25 Aug 2009 (estimated)
- Results
- Posted 19 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the tolerability and side effects of oral sorafenib in combination with intrathecal DepoCyt.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intrathecal DepoCyt and Oral Sorafenib | Experimental | Drug: DepoCyt, Drug: SorafenibThis 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DepoCytAlso: Liposomal Cytarabine, cytarabine liposome injectionPatients were to receive DepoCyt through a reservoir every 2 weeks for 5 doses, then every 4 weeks for an additional 5 doses. | Drug | Intrathecal DepoCyt and Oral Sorafenib |
| SorafenibAlso: Nexavar, BAY 43-9006, oral multi-kinase inhibitorPatients received oral sorafenib at 400 mg twice a day | Drug | Intrathecal DepoCyt and Oral Sorafenib |
Primary outcome
Number of Participants With Adverse Events (AEs)
Time frame: 6 Months
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.
4 secondary outcomes
Number of Participants With Progression Free Survival (PFS) at 6 Months
Time frame: 6 Months
Number of Participants With Overall Survival (OS)
Time frame: 6 Months
Sorafenib Levels in Cerebrospinal Fluid (CSF)
Time frame: 6 Months
CSF and Serum Vascular Endothelial Growth Factor (VEGF) Levels
Time frame: 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Edward Pan, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing DepoCyt and Sorafenib in people with Neoplastic Meningitis, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Adverse Events (AEs) (time frame: 6 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2013.