Intrathecal Gemcitabine to Treat Neoplastic Meningitis, IT Gemcitabine
Subject's are being asked to take part in this study because he or she has a type of cancer that has spread to the meninges (tissues that cover the brain and spinal cord).
There is no known effective treatment for this specific disease or the subject has received all of the treatments that are known to work for his or her specific disease without success. Currently, there is no other effective treatment for this type of cancer.
The purposes of this study are:
- to determine the highest dose of gemcitabine, an anti-cancer drug, that can safely be given directly into the spinal fluid of children and adults whose cancer no longer responds to standard treatment;
- to find out what effects (good and bad) gemcitabine has when given directly into the cerebrospinal fluid (called intrathecal administration) in children and adults with neoplastic meningitis (cancer that has spread to the lining of the brain and spinal cord);
- to determine if gemcitabine is beneficial to the patient;
- to understand how gemcitabine is handled by the body after intrathecal administration.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intrathecal Gemcitabine Therapy for Neoplastic Meningitis: A Phase I and Pharmacokinetic Study|
- Asses the toxicity of intrathecally administered gemcitabine in a limited dosage escalation schedule. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Determination of the maximum tolerated dose of intrathecally administered gemcitabine. [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]The MTD of IT gemcitabine will be that dose at which less than 20% of patients experience DLT as defined earlier. Escalations are planned in groups of three patients, with an additional three patients to be added at the first indication of DLT.
- To define the plasma and CSF pharmacokinetics of gemcitabine and its major metabolite, 2', 2'-difluoro-deoxyuridine (dFdU) after intrathecal administration. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
- Documentation of any responses following intrathecal gemcitabine administration. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
- Investigate MMP expression in pediatric and adult patients with a variety of primary diseases. [ Time Frame: 1 year ] [ Designated as safety issue: No ]
|Study Start Date:||December 2001|
|Study Completion Date:||April 2007|
|Primary Completion Date:||July 2005 (Final data collection date for primary outcome measure)|
Experimental: Intrathecal gemcitabine administration
Intrathecal gemcitabine will be given on a weekly schedule for the first cohort of patients at the 5 mg dose level and then a twice-weekly (i.e., every 3 to 4 days) schedule. Drug administration will be by the intraventricular (Ommaya reservoir injection) route.
Patients will be hospitalized overnight following their first dose of gemcitabine. If the first dose is well tolerated, subsequent induction doses may be administered in the outpatient setting with close observation for a minimum of 2 hours after administration.
Dose Levels and Dose Escalation:
Dose Level 1a: 5 mg
Dose Level 1b: 5 mg
Dose Level 2: 10 mg
Dose Level 3: 20 mg
Dose Level 4: 30 mg
Dose Level 5: 40 mg
Dose Level 6: 50 mg
Induction: At Dose Level 1athe first cohort of patients will receive intrathecal gemcitabine on a weekly basis for a total of 6 weeks. If that is tolerated, the subsequent cohort will receive intrathecal gemcitabine on a twice-weekly basis (Dose Level 1b) for a total of 6 weeks. Subsequent cohorts (Dose Levels 2 - 6) will receive intrathecal gemcitabine on a twice weekly basis for a total of 6 weeks (12 doses).
In the absence of disease progression or DLT, patients may proceed to consolidation.
Consolidation: Intrathecal gemcitabine will be administered weekly for a total of 6 doses. The first dose of consolidation will be given 1 week after the last induction dose. In the absence of disease progression or DLT, patients may proceed to maintenance.
Maintenance: Intrathecal gemcitabine will be given twice monthly for 4 months and monthly thereafter. In the absence of progressive disease or dose-limiting toxicity, the total duration of therapy will be 1 year.
Other Name: Gemzar
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WHAT IS INVOLVED IN THE STUDY? Before participating in this study, there will be a screening process.
Gemcitabine will be received directly into the cerebrospinal fluid (fluid that circulates around the brain and spinal cord) through an Ommaya reservoir (or other similar type of reservoir). An Ommaya reservoir is a surgically implanted catheter that is used to inject medication or to withdraw cerebrospinal fluid from the fluid chambers in the head.
All patients will be hospitalized overnight following their first dose of gemcitabine. If the first dose is well tolerated, further doses of gemcitabine will be administered in the outpatient clinic with close observation for a minimum of 2 hours after administration.
Weeks 1-6 Cohort 1a (first three patients):
Gemcitabine will be given once a week for 6 weeks. Patients may continue therapy if the disease has not worsened.
Weeks 1-6 (all other patients enrolled on this study):
Gemcitabine will be given twice a week for 6 weeks. Patients may continue therapy if the disease has not worsened.
Gemcitabine will be given once a week for 6 weeks.
Weeks 13-29 (approximately):
Gemcitabine will be given twice monthly for 4 months.
Weeks 30-52 (approximately):
Gemcitabine will be given monthly for the duration of the study.
For safety reasons, the first patients treated in the study will receive a low dose of gemcitabine. If that dose does not cause severe side effects, the next group will receive a higher dose of gemcitabine than given to the earlier group, or may receive a lower dose if side effects occur. In addition, the first three patients treated on this study will receive the gemcitabine once weekly. If this is tolerated, subsequent patients will receive the medication twice weekly.
Following the first dose of gemcitabine investigators would like to draw special blood and spinal fluid samples to help learn how much of the drug is in the blood and spinal fluid. These studies are called pharmacokinetics. A total of 10 samples will be collected. The blood samples may be collected from an intravenous catheter or a central venous catheter. The spinal fluid samples may be collected either via Ommaya reservoir or lumbar reservoir.
In addition to intrathecal gemcitabine, the patient may receive other chemotherapy, not given directly into the fluid surrounding the brain and spine, as recommended by his or her doctor for the treatment or prevention of cancer outside the lining of the brain and spinal cord.
The maximum length of treatment with gemcitabine is one year. However, at the end of the study, monthly check-ups are required to monitor the disease and to make sure that any side effects from the study drug have stopped.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00074607
|United States, Maryland|
|National Cancer Institute|
|Bethesda, Maryland, United States, 20892|
|United States, Pennsylvania|
|Children's Hospital of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|University of Pittsburgh Cancer Institute|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Texas|
|Texas Children's Hospital|
|Houston, Texas, United States, 77030|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|Principal Investigator:||Susan Blaney, MD||Baylor College of Medicine|