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”

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. - To assess the pharmokinetics and dosimetry of intrathecal iodine I 124 monoclonal antibody 3F8/PET imaging.

OUTLINE: This is an open-label study.

Patients receive intrathecal iodine I 124 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.

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

PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Intervention(s) in this Clinical Trial

• Other: immunologic technique
• Other: pharmacological study
• Radiation: iodine I 131 monoclonal antibody 3F8

Primary Measures

• Six-month overall survival
  • Safety Issue?: No

DISEASE CHARACTERISTICS:

• Histologically confirmed GD2-expressing malignancy, including the following:
• Medulloblastoma or primitive neuroectodermal tumor of the CNS
• High-grade astrocytoma
• Malignant glioma
• Neuroblastoma
• Retinoblastoma
• Ependymoma
• Rhabdoid tumors
• Sarcomas
• Melanoma
• Small cell lung carcinoma
• Desmoplastic small round cell tumor
• Other tumor types with GD2 expression confirmed by immunohistochemical staining and assessed by the Memorial Sloan-Kettering Department of Pathology using prior frozen tissue, bone marrow, or cerebrospinal fluid cytology
• Must meet 1 of the following criteria:
• Refractory to conventional therapies
• Disease for which no conventional therapy exists
• Recurrent brain tumors with a predilection for leptomeningeal dissemination (e.g., medulloblastoma, supratentorial primitive neuroectodermal tumor, rhabdoid tumor)
• Patients with active malignancy outside the central nervous system are eligible
• No obstructive or symptomatic communicating hydrocephalus

PATIENT CHARACTERISTICS:

• Absolute neutrophil count > 1,000/mm³
• Platelet count > 50,000/mm³
• No uncontrolled life-threatening infection
• No rapidly progressing or deteriorating neurologic examination
• No severe major organ toxicity (i.e., renal, cardiac, hepatic, pulmonary, and gastrointestinal system toxicity ≤ grade 2)
• Stable neurological deficits (due to brain tumor) allowed
• No hearing loss > 3
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No cranial or spinal irradiation within the past 3 weeks
• No prior craniospinal radiation > 45 Gy or focal brain radiation > 72 Gy
• No systemic chemotherapy within the past 3 weeks (corticosteroids allowed)
• Programmable shunt allowed

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Memorial Sloan-Kettering Cancer Center Other

Overall Clinical Trial Officials and Contacts

Kim Kramer, MD Study Chair Memorial Sloan-Kettering Cancer Center  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00445965

Study ID Number: CDR0000534394

ClinicalTrials.gov Identifier: NCT00445965

Health Authority: Unspecified

Clinical trial summary from the National Cancer Institute's PDQ® database