Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Six-month Overall Survival
研究概览
简要总结
RATIONALE: Radiolabeled monoclonal antibodies, such as iodine I 131 monoclonal antibody 3F8, can find tumor cells and carry tumor-killing substances to them without harming normal cells. This may be an effective treatment for central nervous system cancer or leptomeningeal metastases.
PURPOSE: This phase II trial is studying the side effects and how well iodine I 131 monoclonal antibody 3F8 works in treating patients with central nervous system cancer or leptomeningeal cancer.
详细描述
OBJECTIVES:
- Determine if intrathecal iodine I 131 monoclonal antibody 3F8 activity in patients with GD2-expressing central nervous system or leptomeningeal neoplasms is sufficiently promising (i.e., 6-month overall survival rate ≥ 25%) to warrant further study.
- Determine the response rate in patients treated with this drug.
- Determine the cumulative toxicities of this drug in these patients.
- Describe the effects of human-antimouse antibody on cerebrospinal fluid and serum pharmacokinetics in patients treated with this drug.
OUTLINE: This is an open-label study.
Patients receive intrathecal iodine I 131 monoclonal antibody 3F8 for dosimetry. Beginning approximately 1 week later, patients receive intrathecal iodine I 131 monoclonal antibody 3F8 on day 1. Treatment intrathecal iodine I 131 monoclonal antibody 3F8 repeats weekly for up to 4 courses in the absence of disease progression or unacceptable toxicity.
Blood and cerebrospinal fluid samples are collected prior to and after administration of each course of study drug. Samples are analyzed to assess the intrathecal and blood pharmacokinetics of iodine I 131 monoclonal antibody 3F8 and serum human antimouse antibodies. Samples are also analyzed in tumor genetic studies.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have a histologically confirmed diagnosis of a malignancy known to expressGD
- •Such tumors include medulloblastoma/primitive neuroectodermal tumor of the CNS, high grade astrocytomas, malignant glioma, neuroblastoma, retinoblastoma, ependymoma, rhabdoid tumors, sarcomas, melanoma or small cell lung carcinoma. For patients with other tumor types, GD2 expression must be confirmed by immunohistochemical staining and assessed by the Department of Pathology using prior frozen tissue, bone marrow or CSF cytology (send to Research Lab).
- •Patients must have CNS/ leptomeningeal disease including high risk medulloblastoma, or a CNS/leptomeningeal malignancy which is refractory to conventional therapies, or for which no conventional therapy exists, OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, PNET, rhabdoid tumor).
- •Patients must have an absolute neutrophil count (ANC) > 1000/ul and a platelet count > 50,000/ul.
- •Patients may have active malignancy outside the central nervous system.
- •Patients who have a programmable shunt will not be excluded.
- •Both pediatric and adult patients of any age are eligible.
- •Patients or a legal guardian will sign an informed consent form approved by the IRB and obtained by the Principal or a Co- Investigator before patient entry. Minors will provide assent.
排除标准
- •Patients with obstructive or symptomatic communicating hydrocephalus.
- •Patients with an uncontrolled life-threatening infection.
- •Patients who are pregnant: Pregnant women are excluded for fear of danger to the fetus. Therefore negative pregnancy test is required for all women of child-bearing age, and appropriate contraception is required during the study period.
- •Patients who have received cranial or spinal irradiation less than 3 weeks prior to the start of this protocol.
- •Patients who have received systemic chemotherapy (corticosteroids not included) less than 3 weeks prior to the start of this protocol.
- •Severe major organ toxicity. Specifically, renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity should all be less than or equal to grade
- •Patients with stable neurological deficits (because of their brain tumor) are not excluded. Patients with <= 3 hearing loss are not excluded.
- •Patients must have no rapidly progressing or deteriorating neurologic examination.
- •Patients who have already received >45 Gy to the craniospinal radiation or >72 Gy focal brain radiation.
结局指标
主要结局
Six-month Overall Survival
时间窗: 6 months
Number of Participants With Response at 6 Months
时间窗: 6 months
Complete Response (CR): Cytologic and radiographic CR will be evaluated separately, since patients with cytologic clearing and clinical response may continue to have residual abnormalities on MRI scans. Patients with a CR must also have stable or improved neurologic exam. Stable Disease (SD): Exists when a patient fails to fulfill the criteria for either complete or partial response or progressive disease. Progressive Disease (PD): An increase of at least 50% in the absolute number of malignant cells in the CSF OR, in -solid tumor patients, an increase of greater than 25% in the size of measurable lesions on MR scan OR the recurrence of malignant cells in the CSF or new lesions on MR after a patient has attained a complete remission OR evidence of clinical neurologic progression. New sites of or increasing evidence of leptomeningeal enhancement that is not "measurable" will also be considered evidence of disease progression.
次要结局
- Number of Participants Evaluable for Toxicities(1 year)