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

March 7, 2007
March 13, 2015
January 2006
January 2016   (final data collection date for primary outcome measure)
  • 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.
Six-month overall survival
Complete list of historical versions of study NCT00445965 on ClinicalTrials.gov Archive Site
cumulative toxicities [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0).
Not Provided
Not Provided
Not Provided
 
Iodine I 131 Monoclonal Antibody 3F8 in Treating Patients With Central Nervous System Cancer or Leptomeningeal Cancer
Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • 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
    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.
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.
Interventions:
  • Genetic: DNA analysis
  • Other: immunologic technique
  • Other: pharmacological study
  • Radiation: iodine I 131 monoclonal antibody 3F8
  • Radiation: 131I-3F8
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
131
January 2016
January 2016   (final data collection date for primary outcome measure)

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.
Both
Not Provided
No
Contact: Kim Kramer, MD 212-639-6410
Contact: Nai-Kong Cheung, MD, PhD 646-888-2313
United States
 
NCT00445965
05-122, MSKCC-05122
Not Provided
Memorial Sloan Kettering Cancer Center.
Memorial Sloan Kettering Cancer Center.
Not Provided
Study Chair: Kim Kramer, MD Memorial Sloan Kettering Cancer Center.
Memorial Sloan Kettering Cancer Center.
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP