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Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer

Primary Purpose

Brain and Central Nervous System Tumors, Intraocular Melanoma, Lung Cancer

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
DNA analysis
immunologic technique
pharmacological study
iodine I 131 monoclonal antibody 3F8
131I-3F8
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

131I-3F8

Arm Description

This is a phase II single-arm open-label study that will define responses to therapy with weekly intrathecal 131I-3F8 in patients with central nervous system/leptomeningeal GD2-expressing disease.

Outcomes

Primary Outcome Measures

Six-month overall survival
response rate
A "response" is defined as a patient being alive six months after their first treatment.

Secondary Outcome Measures

cumulative toxicities
Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0).

Full Information

First Posted
March 7, 2007
Last Updated
February 1, 2023
Sponsor
Memorial Sloan Kettering Cancer Center
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1. Study Identification

Unique Protocol Identification Number
NCT00445965
Brief Title
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

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
January 2006 (Actual)
Primary Completion Date
February 1, 2023 (Actual)
Study Completion Date
February 1, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Memorial Sloan Kettering Cancer Center

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
78 (Actual)

8. Arms, Groups, and Interventions

Arm Title
131I-3F8
Arm Type
Experimental
Arm Description
This is a phase II single-arm open-label study that will define responses to therapy with weekly intrathecal 131I-3F8 in patients with central nervous system/leptomeningeal GD2-expressing disease.
Intervention Type
Genetic
Intervention Name(s)
DNA analysis
Intervention Type
Other
Intervention Name(s)
immunologic technique
Intervention Type
Other
Intervention Name(s)
pharmacological study
Intervention Type
Radiation
Intervention Name(s)
iodine I 131 monoclonal antibody 3F8
Intervention Type
Radiation
Intervention Name(s)
131I-3F8
Intervention Description
Patients will receive 10mCi intrathecal 131I-3F8 per week. Patients will be pre-medicated with dexamethasone to prevent possible meningeal inflammatory reaction, Liothyronine and SSKI to prevent thyroid accumulation, and acetaminophen and diphenhydramine in anticipation of possible allergic reaction and fever.
Primary Outcome Measure Information:
Title
Six-month overall survival
Time Frame
6 months
Title
response rate
Description
A "response" is defined as a patient being alive six months after their first treatment.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
cumulative toxicities
Description
Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0).
Time Frame
1 year

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kim Kramer, MD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States

12. IPD Sharing Statement

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Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer

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