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Home > "P" Clinical Trials Conditions > Phase I Study of Gemcitabine to Treat Cancer Spread to the Meninges  Phase I Study of Gemcitabine to Treat Cancer Spread to the Meninges
Phase I Study of Gemcitabine to Treat Cancer Spread to the Meninges
For Condition: Meningeal Neoplasms
Status: Recruiting
Sponsor(s): National Cancer Institute (NCI) ,
Synopsis: This study will examine the use of the anti-cancer drug gemcitabine injected intrathecally (into the cerebrospinal fluid, or CSF) to treat cancer that has spread to the meninges (membranes covering the brain and spinal cord). Most anti-cancer drugs that are given by mouth or through a vein do not penetrate the CSF very well; intrathecal administration overcomes this problem. This study will: 1) determine the highest dose of gemcitabine that can safely be given intrathecally to patients with meningeal spread of cancer; 2) examine the side effects and possible benefits of the drug in these patients; and 3) determine how the body absorbs and eliminates the drug. It will also look for a specific protein in the CSF to see if it can be used as a marker to indicate the presence and extent of cancer in the meninges. Patients 3 years of age or older with cancer that has spread to the meninges and who cannot be treated successfully with standard therapy may be eligible for this study. Patients with leukemia in the bone marrow or with blocked CSF flow may not participate. The first patients entering the study will receive a low dose (5 mg) of gemcitabine. The dose will be increased gradually in subsequent small groups of patients as long as it does not cause unacceptable side effects. In addition, the first three patients will receive the drug once a week for the first 6 weeks; if this dose is tolerated, subsequent patients will get the drug twice a week for the first 6 weeks. Weeks 7 through 12, all patients will receive the drug once a week, and weeks 13 to 52 all patients will receive the drug every other week. Additional chemotherapy may be given as needed to treat or prevent cancer outside the meninges. Intrathecal gemcitabine will be delivered by lumbar puncture (spinal tap), Ommaya reservoir, or lumbar reservoir. For lumbar puncture, a local anesthetic is given and a needle is inserted in the space between the bones in the lower back where the CSF circulates below the spinal cord. A small amount of fluid is collected through the needle. An Ommaya reservoir consists of a tube that is placed in a part of the brain containing CSF and is attached to a reservoir implanted under the scalp. A needle can be inserted into the reservoir to inject medication into the CSF or withdraw CSF for examination. A lumbar reservoir is a similar device that is implanted in the lower back. Use of a reservoir is not required for the study. All patients will be hospitalized overnight for the first dose of drug. If this dose is well tolerated, subsequent doses will be given on an outpatient basis with observation for at least 2 hours after administration. After the first dose, blood and CSF samples will be collected to measure levels of gemcitabine in these fluids for studies of how the body handles the drug. Patients will have several tests and procedures before the first dose of gemcitabine and during the treatment period to evaluate the response to treatment and determine drug side effects. These include a medical history and physical and neurological examinations; blood, urine, and CSF tests; and magnetic resonance imaging of the head and possibly the spine. Patients with leukemia or lymphoma and certain solid tumor cancers may have a bone marrow test performed. For this test, the hip area is anesthetized and a special needle is used to draw bone marrow from the hipbone. Patients whose CSF flow is blocked due to the cancer in the meninges will have a scan to look at the flow of fluids in the brain and spine.
Details: The leptomeninges are a common site for the metastatic spread of leukemias, lymphomas, and solid tumors. Because systemically administered drugs penetrate poorly into the CSF, regional (intrathecal) administration is an important component for the prevention and treatment of leptomeningeal tumor spread. Unfortunately, there are only a limited number of anticancer drugs that can be safely administered intrathecally; therefore, new intrathecal agents are needed, especially for solid tumors that metastasize to the meninges. This phase I trial is designed to study the incidence and severity of toxicity from the intrathecal injection of gemcitabine in patients with meningeal cancers that are refractory to conventional therapy; and to identify a safe dose of gemcitabine that can be recommended for intrathecal administration in subsequent phase II trials. The CSF pharmacokinetics of intrathecal gemcitabine will also be studied. The starting dose is 5 mg, with planned escalations to 10, 20, 30, 40, and 50 mg. In the first patient cohort, gemcitabine will be administered intrathecally on a weekly schedule for a six week induction, and subsequent cohorts will be treated twice weekly during induction. The induction is followed by weekly x6 weeks consolidation, twice monthly x4 months and then monthly.
Eligibility:
Study Type: Interventional, Treatment, Safety
Minimum Age/Maximum Age: /
Genders: Both
Protocol Entry Criteria: INCLUSION CRITERIA AGE Patients greater than or equal to 3 years of age at study entry. DIAGNOSIS Patients must have neoplastic meningitis secondary to an underlying leukemia/lymphoma or a solid tumor (including primary CNS tumors or carcinomas of unknown primary site) for which there is no conventional therapy. Patients with CNS leukemia/lymphoma must be refractory to conventional therapy, including XRT (i.e. 2nd or greater relapse). Neoplastic meningitis is defined as follows: 1. Leukemia/Lymphoma - CSF cell count greater than 5/microL AND evidence of blast cells on cytospin preparation or by cytology. 2. Solid tumor - Presence of tumor cells on cytospin preparation or cytology OR presence of meningeal disease on MRI scans. Life Expectancy Patients must have a life expectancy of at least 6 weeks. Performance Status Patients greater than 10 years old should have Karnofsky performance status of greater than or equal to 50 percent and patients less than or equal to 10 years old should have a Lansky performance status of greater than or equal to 50 percent. Patients who are unable to walk because of paralysis, but who are in a wheelchair, will be considered ambulatory for the purposes of the performance score. Recovery from Prior Therapy Patients must have recovered from the acute neurotoxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study and must be without uncontrolled significant systemic illness (e.g.infection). Patients must not have received any systemic CNS-directed therapy within 3 weeks or craniospinal irradiation within 8 weeks prior to starting treatment on this study. Patients must not have received any intrathecal therapy within 1 week prior to starting treatment on this study. Hematologic Status Patients must have a platelet count greater 40,000/mm(3) and Hct greater than 30 percent. Transfusions are allowed to achieve these values, within 48 hours prior to intrathecal gemcitabine treatment. Patients must also have an ANC of greater 1000/microL. Organ Function Patients must have adequate liver function, total bilirubin less than 2.0 mg. percent, SGPT less than 5 times upper limits of normal; adequate renal function (serum creatinine less 2 times upper limits of normal for age). Age Maximum Serum Creatinine (years) less than or equal to age 5 0.8 mg/dl less than age 5 or less than or equal to 10 1.0 mg/dl less than age 10 or less than or equal to 15 1.2 mg/dl greater than age 15 1.5 mg/dl Informed Consent All patients or their legal guardians (if the patient is less than 18 years of age) must sign a document of informed consent according to their institutional guidelines. When appropriate, patients less than18 years of age will be involved in all discussions in order to obtain verbal assent. EXCLUSION CRITERIA Concomitant Therapy: Patients receiving other therapy (either intrathecal or systemic) designed to treat their leptomeningeal disease are not eligible for this study. However, patients receiving concomitant chemotherapy to control systemic disease or bulk CNS disease will be eligible, provided that the systemic chemotherapy is not a phase I agent, an agent that significantly penetrates the CSF [e.g. high-dose methotrexate (greater than 1 g/m2), thiotepa, highdose cytarabine (greater than 1 g/m2), 5-fluorouracil, intravenous 6-mercaptopurine, nitrosoureas, temozolomide, or topotecan], or an agent known to have serious unpredictable CNS side effects. Careful documentation of concurrently administered systemic drugs is required. (Please discuss plans for systemic therapy with the Study Chair or Principal Investigator prior to study entry). Nuclear Medicine CSF Flow Studies: Nuclear Medicine CSF flow studies are required within the 2 weeks prior to study entry for all solid tumor patients. In leukemia/lymphoma patients a CSF flow study is only required if CSF analysis or an MRI suggests that there is a blockage to CSF flow. Patients with clinical evidence of obstructive hydrocephalus are not eligible for this protocol. Nor are patients with compartmentalization of CSF flow as documented by radioisotope Indium111 or Technetium 99-DTPA flow eligible for this protocol. If a CSF flow block or compartmentalization is demonstrated, focal radiotherapy to the site of the block to restore flow followed by a repeat CSF flow study demonstrating clearing of the blockage is required for the patient to be eligible for the study. Patients must not have clinically significant abnormalities of serum electrolytes, including calcium, magnesium, and phosphorus. Patients with a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt are not eligible for this study unless they are shunt-independent and there is evidence that their shunt is nonfunctional (e.g. CSF flow study demonstrating normal flow). Patients who have leukemia/lymphoma with a concomitant bone marrow relapse are not eligible for this study. Women of childbearing age must not be pregnant or lactating. (Male and female patients who are fertile must be must be willing to use an effective means of birth control to avoid pregnancy). Patients must be free of uncontrolled infection except HIV (i.e., AIDS related lymphomatous meningitis). Patients must NOT be receiving any other investigational agents and must not have received any other investigational agent with-in 14 days prior to study treatment. The 14 day period should be extended if the investigational agent is known to have delayed toxicity. Patients with impending spinal cord compression, CNS involvement or requiring local XRT (e.g. optic nerve), are not eligible for this study. Concomitant CNS radiation therapy is not permitted. (Patients are not permitted to receive radiation to any port that encompasses any part of the brain or spine while on study.) Patients may receive radiation therapy to extra-CNS sites, e.g. painful bone metastases not in the craniospinal axis.
Total Enrollment: 30
Location and Contact Information:
National Cancer Institute (NCI) *Recruiting*
Bethesda, Maryland, 20892
United States
Recruiting Patient and Public Liaison Office 1-800-411-1222
Additional Information:
Study ID Numbers: 030032; 03-C-0032
Study Start Date: October 25, 2002
Record last reviewed: October 7, 2003
Additional information available at: clinicaltrials.gov
Clinicaltrials.gov Reference link: NCT00048243
Other Meningeal Neoplasms Studies:
1. Phase I Study of Gemcitabine to Treat Cancer Spread to the Meninges
2. DepoCyt Therapy in Patients with Neoplastic Meningitis from Lymphoma or a Solid Tumor
3. Phase I Study of Intrathecal Topotecan
Related Studies:
Other Meningeal Neoplasms Clinical Trials
Other Maryland Clinical Trials
Other Bethesda Clinical Trials
Phase I Study of Gemcitabine to Treat Cancer Spread to the Meninges
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