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

Lung Cancer Clinical Trial

Official title:

Phase II Study of Intrathecal I-3F8 in Patients With GD2-Expressing Central Nervous System and Leptomeningeal Neoplasms

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445965
• Other study ID #: 05-122
• Secondary ID: MSKCC-05122
• Status: Completed
• Phase: Phase 2
• Start date: January 2006
• Est. completion date: February 1, 2023

Study information

• Verified date: February 2023
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 78
• Est. completion date: February 1, 2023
• Est. primary completion date: February 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Intestinal Neoplasms
• Intraocular Melanoma
• Lung Cancer
• Lung Neoplasms
• Melanoma
• Melanoma (Skin)
• Metastatic Cancer
• Nervous System Neoplasms
• Neuroblastoma
• Ovarian Cancer
• Retinoblastoma
• Sarcoma
• Small Intestine Cancer

Intervention

Genetic:
• DNA analysis

Other:
• immunologic technique

• pharmacological study

Radiation:
• iodine I 131 monoclonal antibody 3F8

• 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.

Locations

Country	Name	City	State
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Six-month Overall Survival		6 months
Primary	Number of Participants With Response at 6 Months	Complete Response (CR): Cytologic and radiographic CR will be evaluated separately, since patients with cytologic clearing and clinical response may continue to have residual abnormalities on MRI scans. Patients with a CR must also have stable or improved neurologic exam.; Stable Disease (SD): Exists when a patient fails to fulfill the criteria for either complete or partial response or progressive disease.; Progressive Disease (PD): An increase of at least 50% in the absolute number of malignant cells in the CSF OR, in -solid tumor patients, an increase of greater than 25% in the size of measurable lesions on MR scan OR the recurrence of malignant cells in the CSF or new lesions on MR after a patient has attained a complete remission OR evidence of clinical neurologic progression. New sites of or increasing evidence of leptomeningeal enhancement that is not "measurable" will also be considered evidence of disease progression.	6 months
Secondary	Number of Participants Evaluable for Toxicities	Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0).	1 year