Monoclonal Antibody Therapy in Treating Patients With Leptomeningeal Cancer

Memorial Sloan Kettering Cancer Center (MSK)

Status and phase: Completed; Phase 1

Conditions: Sarcoma; Neuroblastoma; Brain and Central Nervous System Tumors; Melanoma (Skin); Intraocular Melanoma; Lung Cancer; Retinoblastoma

Treatments: Radiation: iodine I 131 monoclonal antibody 3F8

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00003022

NCI-G97-1267

CDR0000065607 (Registry Identifier)

97-021

Details and patient eligibility

About

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of monoclonal antibody therapy in treating patients who have leptomeningeal metastases.

Full description

OBJECTIVES:

• Define the clinical toxicities of intrathecal iodine I 131 monoclonal antibody 3F8 (I-3F8) in patients with GD2 positive leptomeningeal neoplasms.
• Determine whether I-3F8 can detect GD2 positive leptomeningeal tumors.
• Measure the cerebrospinal fluid (CSF) levels and serum pharmacokinetics of I-3F8 in these patients.

OUTLINE: This is a dose escalation study.

Patients receive a single injection of intraventricular or intrathecal iodine I 131 monoclonal antibody 3F8. Patients without objective disease progression and no grade 3 or 4 toxicity 6 weeks after the first dose may receive a second injection.

Cohorts of at least 3 patients are entered at escalating doses of I-3F8. If grade 3 or worse toxicity occurs in 1 or more of 3 patients at a given dose level, then 3 additional patients are accrued at that level. If 2 or more of 6 patients at a given dose level experience grade 3 or worse toxicity, then that dose is declared the maximum tolerated dose (MTD).

Patients are followed weekly for 4 weeks.

PROJECTED ACCRUAL: Approximately 3-30 patients will be accrued for this study over 2-3 years.

Sex: All

Ages: 3+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy expressing GD2, including, but not limited to:

  • Medulloblastoma/primitive neuroectodermal tumor of the CNS
  • Malignant glioma
  • Neuroblastoma
  • Retinoblastoma
  • Ependymoma
  • Sarcoma
  • Melanoma
  • Small cell lung carcinoma
  • Other tumor types must have GD2 expression confirmed by immunohistochemical staining

• Cerebrospinal fluid or leptomeningeal disease that is refractory to conventional therapy or for which no conventional therapy exists

• Prior measurable human anti-mouse monoclonal antibody titer allowed

PATIENT CHARACTERISTICS:

Age:

• 3 and over

Performance status:

• Not specified

Life expectancy:

• At least 2 months

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 50,000/mm^3

Hepatic:

• Bilirubin less than 3 mg/dL

Renal:

• Creatinine less than 2 mg/dL
• Blood urea nitrogen less than 30 mg/dL

Other:

• May have active malignancy outside the central nervous system
• No obstructive hydrocephalus
• No CNS grade 3 or 4 toxicity as a consequence of prior treatments
• No life threatening infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Prior monoclonal antibody treatment allowed

Chemotherapy:

• Prior chemotherapy allowed
• Must have recovered from all hematopoietic and neurologic side effects of prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• Prior radiotherapy allowed
• At least 6 weeks since prior cranial or spinal irradiation

Surgery:

• Not specified