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.
Active, not recruiting
Phase 2
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 131I-3F8 | Experimental | 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. |
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Six-month overall survival |
| Time Frame: | 6 months |
| Safety Issue: | |
| Description: | A "response" is defined as a patient being alive six months after their first treatment. |
| Measure: | cumulative toxicities |
| Time Frame: | 1 year |
| Safety Issue: | |
| Description: | Toxicities will be assessed via the NCI toxicity criteria (CTC 3.0). |
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Active, not recruiting |
| Lead Sponsor: | Memorial Sloan Kettering Cancer Center |
October 29, 2020
