Clinical trial NCT00003022: Monoclonal Antibody Therapy in Treating Patients With Leptomeningeal Cancer
Official title: Phase I Study of Intrathecal 131-I-3F8 Monoclonal Antibody in Patients With GD2 Positive Leptomeningeal Neoplasms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Intraocular Melanoma
Lung Cancer
Melanoma (Skin)
Neuroblastoma
Retinoblastoma
Sarcoma
Keywords: metastatic osteosarcoma
childhood infratentorial ependymoma
recurrent childhood rhabdomyosarcoma
childhood supratentorial ependymoma
regional neuroblastoma
disseminated neuroblastoma
stage 4S neuroblastoma
recurrent neuroblastoma
retinoblastoma
intraocular retinoblastoma
extraocular retinoblastoma
recurrent retinoblastoma
extensive stage small cell lung cancer
recurrent small cell lung cancer
recurrent osteosarcoma
recurrent adult brain tumor
iris melanoma
ciliary body and choroid melanoma, small size
ciliary body and choroid melanoma, medium/large size
extraocular extension melanoma
recurrent intraocular melanoma
adult brain stem glioma
adult medulloblastoma
stage IV melanoma
recurrent melanoma
metastatic childhood soft tissue sarcoma
recurrent childhood soft tissue sarcoma
adult myxopapillary ependymoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
adult mixed glioma
localized unresectable neuroblastoma
adult ependymoblastoma
recurrent childhood brain stem glioma
recurrent childhood supratentorial primitive neuroectodermal tumor
recurrent childhood visual pathway glioma
recurrent childhood medulloblastoma
recurrent childhood visual pathway and hypothalamic glioma
previously treated childhood rhabdomyosarcoma
localized Ewing sarcoma/peripheral primitive neuroectodermal tumor
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent childhood ependymoma
adult oligodendroglioma
adult anaplastic astrocytoma
adult supratentorial primitive neuroectodermal tumor (PNET)
adult diffuse astrocytoma
adult pilocytic astrocytoma
adult giant cell glioblastoma
adult glioblastoma
adult gliosarcoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan-Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Kim Kramer, MD
role: STUDY_CHAIR
References:
citation: Kramer K, Humm JL, Souweidane MM, Zanzonico PB, Dunkel IJ, Gerald WL, Khakoo Y, Yeh SD, Yeung HW, Finn RD, Wolden SL, Larson SM, Cheung NK. Phase I study of targeted radioimmunotherapy for leptomeningeal cancers using intra-Ommaya 131-I-3F8. J Clin Oncol. 2007 Dec 1;25(34):5465-70. doi: 10.1200/JCO.2007.11.1807.