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

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:

Genetics Home Reference related topics: Ewing sarcoma neuroblastoma retinoblastoma

MedlinePlus related topics: Cancer Intestinal Cancer Lung Cancer Melanoma Neuroblastoma Ovarian Cancer Soft Tissue Sarcoma

Drug Information available for: Iodine Sodium iodide I 131 Iodide

U.S. FDA Resources

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:	77
Study Start Date:	January 2006
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	January 2014 (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.

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

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

Contacts and Locations

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:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

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:	February 26, 2013
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:

Duodenal Neoplasms
Lung Neoplasms
Melanoma
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Nervous System Neoplasms
Neuroblastoma
Ovarian Neoplasms
Retinoblastoma
Central Nervous System Neoplasms
Ileal Neoplasms
Jejunal Neoplasms
Astrocytoma
Neuroectodermal Tumors, Primitive

Uveal Neoplasms
Desmoplastic Small Round Cell Tumor
Intestinal Neoplasms
Neuroectodermal Tumors, Primitive, Peripheral
Meningeal Neoplasms
Sarcoma
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on May 21, 2013