Clinical trial NCT00445965: Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer
Official title: Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Brain and Central Nervous System Tumors
Intraocular Melanoma
Lung Cancer
Melanoma (Skin)
Metastatic Cancer
Neuroblastoma
Ovarian Cancer
Retinoblastoma
Sarcoma
Small Intestine Cancer
Keywords: recurrent childhood medulloblastoma
untreated childhood medulloblastoma
adult supratentorial primitive neuroectodermal tumor (PNET)
recurrent childhood supratentorial primitive neuroectodermal tumor
untreated childhood supratentorial primitive neuroectodermal tumor
adult anaplastic astrocytoma
adult diffuse astrocytoma
adult pilocytic astrocytoma
adult subependymal giant cell astrocytoma
recurrent childhood subependymal giant cell astrocytoma
untreated childhood subependymal giant cell astrocytoma
recurrent childhood cerebellar astrocytoma
recurrent childhood cerebral astrocytoma
untreated childhood cerebellar astrocytoma
adult brain stem glioma
adult mixed glioma
childhood mixed glioma
recurrent childhood brain stem glioma
recurrent childhood visual pathway and hypothalamic glioma
recurrent childhood visual pathway glioma
untreated childhood brain stem glioma
untreated childhood visual pathway and hypothalamic glioma
untreated childhood visual pathway glioma
regional neuroblastoma
disseminated neuroblastoma
recurrent neuroblastoma
extraocular retinoblastoma
recurrent retinoblastoma
adult anaplastic ependymoma
adult ependymoblastoma
adult ependymoma
adult myxopapillary ependymoma
adult subependymoma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
recurrent childhood ependymoma
childhood atypical teratoid/rhabdoid tumor
recurrent melanoma
stage IV melanoma
adult medulloblastoma
chondrosarcoma
metastatic osteosarcoma
recurrent osteosarcoma
metastatic childhood soft tissue sarcoma
ovarian sarcoma
recurrent childhood soft tissue sarcoma
stage III adult soft tissue sarcoma
stage IV adult soft tissue sarcoma
stage III uterine sarcoma
stage IV uterine sarcoma
previously treated childhood rhabdomyosarcoma
recurrent childhood rhabdomyosarcoma
adult anaplastic oligodendroglioma
adult desmoplastic small round cell tumor
adult oligodendroglioma
adult giant cell glioblastoma
adult gliosarcoma
tumors metastatic to brain
adult rhabdomyosarcoma
childhood oligodendroglioma
childhood desmoplastic small round cell tumor
extensive stage small cell lung cancer
intraocular retinoblastoma
recurrent adult brain tumor
recurrent adult soft tissue sarcoma
recurrent uterine sarcoma
small intestine leiomyosarcoma
recurrent small intestine cancer
recurrent small cell lung cancer
extraocular extension melanoma
recurrent intraocular melanoma
metastatic intraocular melanoma
iris melanoma
ciliary body and choroid melanoma, medium/large size
newly diagnosed childhood ependymoma
adult glioblastoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent childhood pineoblastoma
untreated childhood pineoblastoma
adult pineal gland astrocytoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma
recurrent childhood anaplastic astrocytoma
untreated childhood anaplastic astrocytoma
recurrent childhood anaplastic oligoastrocytoma
recurrent childhood anaplastic oligodendroglioma
untreated childhood anaplastic oligoastrocytoma
untreated childhood anaplastic oligodendroglioma
recurrent childhood giant cell glioblastoma
recurrent childhood glioblastoma
untreated childhood giant cell glioblastoma
untreated childhood glioblastoma
recurrent childhood gliosarcoma
untreated childhood gliosarcoma
recurrent childhood gliomatosis cerebri
untreated childhood gliomatosis cerebri
childhood high-grade cerebellar astrocytoma
childhood high-grade cerebral astrocytoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
First posted: 2007-03-09
Enrollment: 78
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

After completion of study treatment, patients are followed periodically for 3 months.

Eligibility criteria: Inclusion Criteria:

* Patients must have a histologically confirmed diagnosis of a malignancy known to expressGD2. 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.

Exclusion Criteria:

* 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 2. 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.

Primary outcomes:
measure: Six-month Overall Survival
timeFrame: 6 months
measure: Number of Participants With Response at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Number of Participants Evaluable for Toxicities
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Kim Kramer, MD
role: STUDY_CHAIR
References: