Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Radiolabeled Monoclonal Antibody Therapy in Treating Patients With Refractory, Recurrent, or Advanced CNS or Leptomeningeal Cancer

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Active Any age NCI MSKCC-03133 NCT00089245

Objectives

1. Determine the maximum tolerated dose of intrathecal iodine I 131 monoclonal antibody 8H9 in patients with refractory, recurrent, or advanced CNS or leptomeningeal cancer.
2. Determine the clinical toxic effects of this drug in these patients.
3. Determine the pharmacokinetics and dosimetry of this drug in these patients.
4. Correlate tumor response by MRI with CSF reverse-transcription polymerase chain reaction in patients treated with this drug.

Entry Criteria

Disease Characteristics:

• Histologically confirmed CNS or leptomeningeal cancer, meeting 1 of the following criteria:
  • Refractory to conventional therapy OR for which no conventional therapy exists
    • Less than 10% chance of cure with conventional therapy
  • Recurrent brain tumor or other solid tumor with a predilection for leptomeningeal dissemination, including, but not limited to, the following:
    • Medulloblastoma
    • Ewing's sarcoma/primitive neuroectodermal tumor
    • Rhabdoid tumor
    • Neuroblastoma
    • Osteosarcoma
    • Desmoplastic small rounded-cell tumor
    • Rhabdomyosarcoma



• 8H9 reactivity confirmed by immunohistochemical staining



• No rapidly progressing or deteriorating neurologic examination
  • Stable neurological deficits as a result of brain tumor allowed



• No obstructive or symptomatic communicating hydrocephalus

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• At least 3 weeks since prior systemic chemotherapy

Endocrine therapy

• Prior corticosteroids allowed

Radiotherapy

• At least 3 weeks since prior cranial or spinal radiotherapy

Surgery

• Not specified

Patient Characteristics:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 1,000/mm³
• Platelet count > 50,000/mm³

Hepatic

• No hepatic toxicity ≥ grade 2

Renal

• No renal toxicity ≥ grade 2

Cardiovascular

• No cardiac toxicity ≥ grade 2

Pulmonary

• No pulmonary toxicity ≥ grade 2

Other

• Not pregnant or nursing
• Negative pregnancy test
• Concurrent active malignancy outside the CNS allowed
• No uncontrolled life-threatening infection
• No gastrointestinal system toxicity ≥ grade 2
• No other severe major organ toxicity
  • Hearing loss ≤ grade 3

Expected Enrollment

A total of 3-30 patients will be accrued for this study within 2-3 years.

Outline

This is a dose-escalation study.

Patients receive iodine I 131 monoclonal antibody 8H9 (¹³¹I MOAB 8H9) intrathecally on day 1. Treatment repeats every 4 weeks for up to 2 courses (total of 2 injections) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of ¹³¹I MOAB 8H9 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Trial Contact Information

Trial Lead Organizations

Memorial Sloan-Kettering Cancer Center

Kim Kramer, MD, Protocol chair		Ph: 212-639-6410; 800-525-2225 Email: kramerk@mskcc.org

U.S.A.
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Kim Kramer, MD	Ph:  212-639-6410 800-525-2225
			Email: kramerk@mskcc.org
		Nai-Kong Cheung, MD, PhD	Ph:  212-639-8401 800-525-2225

Registry Information
Official Title		Phase I Study Of Inthrathecal Radioimmunotherapy Using 131I-8H9 For Central Nervous System/Leptomeningeal Neoplasms
Trial Start Date		2004-07-02
Trial Completion Date		2010-07-02 (estimated)
Registered in ClinicalTrials.gov		NCT00089245
Date Submitted to PDQ		2004-07-02
Information Last Verified		2008-03-30
NCI Grant/Contract Number		P30-CA08748