Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase I Treatment Closed physiologic 70 or less MDA-DM-88141 NCI-B88-0015, B88-0015

Objectives

I.  Determine the maximum tolerated dose and toxicity of murine monoclonal 
antibody 14G2A (MoAb 14G2A) administered by a 5-day continuous intravenous 
infusion in patients with malignant melanoma, small cell carcinoma of the 
lung, osteosarcoma, or neuroblastoma.
II.  Study the pharmacokinetics and biodistribution of iodine-131 radiolabeled 
and unlabeled MoAb 14G2A.
III.  Quantitate the degree of tumor uptake of MoAb 14G2A, determine effector 
cell phenotype, and measure tumor binding lymphocytes against autologous tumor 
in selected patients for whom excisional biopsies can be performed.
IV.  Measure various immunologic parameters in peripheral blood, including 
serum complement levels, lymphocyte markers, antibody-dependent cell-mediated 
cytotoxicity, and complement-dependent toxicity against a melanoma cell line.
V.  Measure human antimouse antibody responses, and determine whether 
immunologic tolerance occurs with dose escalation.
VI.  Document the antitumor activity of MoAb 14G2A in this patient population.

Entry Criteria

Disease Characteristics:

See General Eligibility Criteria

Patient Characteristics:

See General Eligibility Criteria

General Eligibility Criteria:

Patients no more than physiologic 70 
years of age with a histologically proven primary diagnosis of malignant 
melanoma, small cell carcinoma of the lung, osteosarcoma, or neuroblastoma who 
have failed or are incurable by standard treatment.  Evaluable metastatic 
disease is required, but patients with CNS metastases are ineligible.  At 
least 3 weeks must have elapsed since prior chemotherapy (6 weeks since 
mitomycin-C and nitrosoureas), immunotherapy, or radiotherapy; no prior 
administration of murine immunoglobulins for imaging or treatment is allowed, 
and patients must have no history of iodine allergy.  Patients who have had 
prior surgery must be fully recovered.  An ambulatory performance status 
(Karnofsky 60% or better) and a minimum life expectancy of 3 months are 
required, as is adequate organ function documented as follows:  WBC at least 
4,000, granulocytes greater than 2,000, and platelets at least 100,000; 
biliburin no more than 1.5 mg/dl; creatinine no more than 2.0 mg/dl or 
creatinine clearance at least 60 ml/minute and proteinuria no more than 2+; 
and PT less than 14 seconds and PTT less than 35 seconds.  Patients with NYHA 
class III/IV cardiac disease, angina, myocardial infarction, or arrhythmias 
are excluded; in the presence of suspected cardiac dysfunction (e.g., 
conduction defects on EKG), patients must have a normal stress test.  The 
following conditions also exclude:  serious active infection or other serious 
intercurrent illness; known seizure disorder; requirement for corticosteroids 
or nonsteroidal anti-inflammatory agents; and seropositive HBsAg or HIV 
antibody test.  Fertile women must use effective contraception; pregnancy and 
lactation exclude.

Expected Enrollment

25-30 patients will be studied.  An accrual rate of 6 patients per month is 
anticipated, with an estimated 10 months required for completion of the study.

Outline

Nonrandomized study.
Monoclonal Antibody Therapy.  Murine Anti-GD2 Ganglioside Monoclonal Antibody 
14G2A, MoAb 14G2A, NSC-624345.

Murray JL, Cunningham JE, Brewer H, et al.: Phase I trial of murine monoclonal antibody 14G2a administered by prolonged intravenous infusion in patients with neuroectodermal tumors. J Clin Oncol 12 (1): 184-93, 1994.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

J. Lee Murray, MD, Protocol chair		Ph: 713-792-4561; 800-392-1611 Email: jmurray@mdanderson.org