Phase I Study of Temozolomide and Intrathecal DepoCyt in Patients With Neoplastic Meningitis
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD) for the combination of Temozolomide and DepoCyt
研究概览
简要总结
Objectives:
- To determine the safety, tolerability and maximum tolerated dose (MTD) of oral temozolomide using a 7 days on and 7 days off regimen combined with intrathecal liposomal cytarabine (DepoCyt) in patients with neoplastic meningitis from solid tumors and systemic lymphoma.
详细描述
Liposomal cytarabine is a slow-release formulation of cytarabine or Ara-C. It is designed to slowly release cytarabine to increase exposure of cancer cells to the drug in the treatment of leptomeningeal disease. Temozolomide is a chemotherapy drug that is designed to attach to the DNA of rapidly dividing cells (cancer cells). The cells recognize this and self-destruct.
Tests called an Indium-111 or Technetium 99m-DPTA CSF flow study, where radioactive dye is injected into the CSF, will be done to make sure the CSF flows freely throughout the spinal canal. These are done as part of the screening evaluation. If the flow study is okay, you will be eligible to take part in this study. But if there is a block of the CSF pathway, the area may be treated (usually with radiation) and then you can be re-evaluated and may still be enrolled in the study if a repeat flow study shows that the block has been cleared.
If you have a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt in place, you will have a shunt closure test in which your shunt system will be closed and you will be monitored for 4 hours for the development of clinical signs of increased intracranial pressure. The shunt closure test is performed to allow for a long enough time for the shunt to be closed after liposomal cytarabine is injected. Researchers want to make sure that the drug will stay in the CSF system long enough to perform its function, without being siphoned off through the shunt.
An Ommaya Reservoir (a small round plastic pouch with a tube that goes into the brain and CSF) will be placed under the scalp by a neurosurgeon before starting therapy if you do not already have one in place. The reservoir will be used to deliver the liposomal cytarabine and to collect samples of CSF when they are needed.
Liposomal cytarabine will be given through the Ommaya Reservoir once every 14 days on Day 1 for a total of 12 weeks (6 treatments). This is called Induction Treatment. After the first 12 weeks, liposomal cytarabine will be given on Day 1 every 28 days for 40 weeks (10 treatments). This is called Maintenance Treatment. If you are not already taking daily dexamethasone, you will begin to take dexamethasone by mouth twice a day on the day before the depocyt starts each course and continuing 5 days after the administration of liposomal cytarabine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be >/=18 years of age
- •All patients with the exception of those with primary brain tumors, must have histologic diagnosis of systemic malignancy. Patients must have the presence of malignant cells in CSF (+CSF) or clinical signs and symptoms of leptomeningeal disease and radiographic abnormalities without malignant cells identified in the CSF (-CSF). Clinical signs/symptoms include cerebral hemispheric, cranial nerve, and/or spinal cord/root dysfunction.
- •Patients must have Karnofsky performance status of >/=60%. Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purposes of the performance score.
- •Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy, before entering the study and must be without significant systemic illness. Patients must not have received any systemic therapy for Leptomeningeal disease (LMD) within 3 wks (6 wks if a nitrosourea), intrathecal chemotherapy within 1 wk, or irradiation within 8 wks prior to treatment on this study. Patients previously receiving craniospinal irradiation must have positive cytology or progression of meningeal disease on MRI scan. Patients must not have received whole brain or focal CNS radiotherapy within 1 wk of treatment.
- •Patients must have a platelet count >/= 75,000/mm(3) and ANC >/= 1500/mm(3) within 72 hours prior to intrathecal DepoCyt and temozolomide treatment.
- •Patients must have adequate liver function, total bilirubin < 2.0 mg%; SGPT < 5 times normal; adequate renal function (serum creatinine </= 1.5 mg); and normal metabolic parameters (serum electrolytes, calcium, magnesium, and phosphorus).
- •All patients or their legal guardians must sign a document of informed consent indicating their awareness of the investigational nature and the risks of this study.
- •Ventricular access devices (e.g. an Ommaya reservoir) are mandatory.
排除标准
- •Patients receiving other therapy (either intrathecal or systemic) designed specifically to treat their leptomeningeal disease are not eligible for this study. However, patients receiving concomitant non-cytotoxic therapy (hormonal or cytostatic therapy) to control systemic disease or bulk CNS disease will be eligible, provided the therapy is not a phase I agent, an agent which significantly penetrates the CSF or an agent known to have serious unpredictable CNS side effects.
- •continued) No other cytotoxic chemotherapies are allowed (non-cytotoxic therapies such as herceptin, tarceva, arimidex etc are allowed at the investigator's discretion). Careful documentation of concurrently administered systemic drugs is required.
- •Patients with clinical evidence of obstructive hydrocephalus or compartmentalization of the CSF flow as documented by radioisotope Indium-(111) (Technetium(99) -DTPA when Indium-(111) unavailable) flow study are not eligible for this protocol. CSF obstruction will be determined by routine nuclear medicine CSF flow study parameters. If patients have evidence of block that is subsequently proven to be relieved after focal XRT, these patients can enroll immediately after repeat flow study shows block to be relieved.
- •Patients with a ventriculoperitoneal (VP) or ventriculoatrial (VA) shunt must have an on/off device in their shunt systems to be eligible for the study. Patients must be able to tolerate shunt closure for >/= 4 hours without development of clinical signs of increased intracranial pressure. Patients unable to tolerate shunt closure for >/= 4 hours will not be eligible for the study.
- •Women of childbearing potential (females who are not surgically sterile or who have had a period in the last 12 months) must have a negative serum pregnancy test and must not be lactating.
- •Patients with any uncontrolled infection (life-threatening infection resistant to treatment after 7 days) are not eligible for this study, except those with HIV and AIDS-related lymphomatous meningitis).
- •Use of any other investigational drug within 7 days prior to study entry. This period should be extended if the patient has received any investigational agent that is known to have delayed toxicities after 7 days or a prolonged half-life.
- •Patients not able to undergo magnetic resonance testing. i.e. pacemaker.
- •Patients may not have had prior treatment with Temozolomide.
研究组 & 干预措施
DepoCyt + Temozolomide
DepoCyt Starting 50 mg Intrathecal Day 1 every 14 days for 12 weeks (6 treatments), then every 28 days for 40 weeks (10 treatments). Temozolomide 100 mg/m^2 by mouth daily for 7 days every 14 days.
干预措施: DepoCyt (Drug)
DepoCyt + Temozolomide
DepoCyt Starting 50 mg Intrathecal Day 1 every 14 days for 12 weeks (6 treatments), then every 28 days for 40 weeks (10 treatments). Temozolomide 100 mg/m^2 by mouth daily for 7 days every 14 days.
干预措施: Temozolomide (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) for the combination of Temozolomide and DepoCyt
时间窗: 28 days
The MTD is the dose at which 0/3 or 1/6 participants experience Dose Limiting Toxicity (DLT) with the next higher dose having at least 2/3 or 2/6 participants encountering DLT. MTD based on the assessment of DLT during the first 28 days of treatment on the regimen.
次要结局
未报告次要终点