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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Memorial Sloan Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00445965
First received: March 7, 2007
Last updated: March 13, 2015
Last verified: March 2015
  Purpose

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.


Condition Intervention Phase
Brain and Central Nervous System Tumors
Intraocular Melanoma
Lung Cancer
Melanoma (Skin)
Metastatic Cancer
Neuroblastoma
Ovarian Cancer
Retinoblastoma
Sarcoma
Small Intestine Cancer
Genetic: DNA analysis
Other: immunologic technique
Other: pharmacological study
Radiation: iodine I 131 monoclonal antibody 3F8
Radiation: 131I-3F8
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • Six-month overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    A "response" is defined as a patient being alive six months after their first treatment.


Secondary Outcome Measures:
  • cumulative toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0).


Estimated Enrollment: 131
Study Start Date: January 2006
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 131I-3F8
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.
Genetic: DNA analysis Other: immunologic technique Other: pharmacological study Radiation: iodine I 131 monoclonal antibody 3F8 Radiation: 131I-3F8
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.

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00445965

Contacts
Contact: Kim Kramer, MD 212-639-6410
Contact: Nai-Kong Cheung, MD, PhD 646-888-2313

Locations
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Kim Kramer, MD    212-639-6410      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Investigators
Study Chair: Kim Kramer, MD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00445965     History of Changes
Other Study ID Numbers: 05-122, MSKCC-05122
Study First Received: March 7, 2007
Last Updated: March 13, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan Kettering Cancer Center:
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

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Melanoma
Neoplasm Metastasis
Nervous System Neoplasms
Neuroblastoma
Retinoblastoma
Uveal Neoplasms
Eye Diseases
Eye Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Neuroepithelial
Neoplastic Processes
Nervous System Diseases
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neuroendocrine Tumors
Nevi and Melanomas
Pathologic Processes
Retinal Diseases
Retinal Neoplasms
Uveal Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors

ClinicalTrials.gov processed this record on April 23, 2015