Monoclonal Antibody Therapy Plus Etoposide in Treating Patients With Neuroblastoma
Information source: National Cancer Institute (NCI)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Neuroblastoma
Intervention: etoposide (Drug); isotretinoin (Drug); monoclonal antibody 3F8 (Drug)
Phase: Phase 2
Status: Active, not recruiting
Sponsored by: Memorial Sloan-Kettering Cancer Center Official(s) and/or principal investigator(s):
Nai-Kong V. Cheung, MD, PhD, Study Chair, Affiliation: Memorial Sloan-Kettering Cancer Center
Summary
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor
killing substances to them without harming normal cells. Drugs used in chemotherapy use
different ways to stop tumor cells from dividing so they stop growing or die. Combining
monoclonal antibody therapy with chemotherapy may kill more tumor cells.
PURPOSE: Phase II trial to study the effectiveness of monoclonal antibody therapy plus
etoposide in treating patients who have neuroblastoma.
Clinical Details
Official title: Monoclonal Antibody 3F8 and Oral Etoposide for the Treatment of Neuroblastoma
Study design: Treatment, Open Label
Detailed description:
OBJECTIVES:
- Determine the antitumor effects of monoclonal antibody 3F8, etoposide, and isotretinoin
using standard imaging methods and tumor marker studies in patients with high-risk
neuroblastoma.
- Assess progression-free survival in these patients after this treatment.
- Assess the effects of oral etoposide on human anti-mouse antibody and anti-idiotype
response in these patients.
OUTLINE: Patients are stratified according to disease status (evaluable but not measurable vs
second or subsequent remission with no measurable or evaluable disease).
Patients receive monoclonal antibody 3F8 (MOAB 3F8) IV over 1. 5 hours once daily on days 1-10
and oral etoposide once daily on days 29-49. Treatment repeats every 8 weeks for 4 courses in
the absence of disease progression, human anti-mouse antibody (HAMA) response, or
unacceptable toxicity.
If HAMA fails to develop after completion of 4 courses of MOAB 3F8, patients continue
treatment with MOAB 3F8 on days 1-5 every 8 weeks until HAMA reaches greater than 1,000 U/mL
or until month 24, whichever occurs first.
Beginning after completion of 4 courses of etoposide and MOAB 3F8 or if HAMA develops,
patients receive oral isotretinoin twice daily for 14 days followed by at least a 14-day
rest. Treatment repeats for a total of 6 courses.
PROJECTED ACCRUAL: A total of 50 patients (25 per stratum) will be accrued for this study
within 5 years.
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
Criteria:
DISEASE CHARACTERISTICS:
- High-risk neuroblastoma by:
- Histopathology OR
- Bone marrow involvement plus elevated urinary catecholamines
- Prior tumor progression on standard chemotherapy and poor long-term prognosis as
indicated by 1 or more of the following:
- N-myc amplification in tumor cells
- Diploid chromosomal content plus lp loss of heterozygosity in tumor cells
- Distant skeletal metastases
- Unresectable primary tumor infiltrating across the midline
- More than 10% tumor cells in bone marrow
- Less than 30% chance of long-term progression-free survival
- Evaluable (microscopic marrow metastasis, elevated tumor markers, abnormal bone scan
or MIBG or PET scan) but not measurable (CT scan, MRI) disease documented at least 4
weeks after completion of prior systemic therapy
- No rapidly progressive disease as defined by 1 or more of the following:
- Serum lactic dehydrogenase greater than 1. 5 times upper limit of normal due to
tumor
- An opiate requirement for pain from tumor
- Greater than 25% increase in tumor by successive imaging studies
- Life expectancy less than 8 weeks
- Second or subsequent remission after chemotherapy and/or radiotherapy allowed provided
there is less than 30% chance of survival
- No prior myelodysplastic syndromes or leukemia
PATIENT CHARACTERISTICS:
Age:
- Not specified
Performance status:
- Not specified
Life expectancy:
- See Disease Characteristics
- At least 8 weeks
Hematopoietic:
- Not specified
Hepatic:
- No grade 3 or worse liver toxicity
Renal:
- No grade 3 or worse renal toxicity
- Creatinine clearance at least 60 mL/min
Cardiovascular:
- No grade 3 or worse cardiac toxicity
Pulmonary:
- No grade 3 or worse pulmonary toxicity
Other:
- Not pregnant
- No grade 3 or worse gastrointestinal toxicity
- No grade 3 or worse neurologic system toxicity
- No grade 4 hearing deficit
- No active life-threatening infection
- No prior exposure to mouse antibodies and human anti-mouse antibody greater than 1,000
ELISA units/mL
- No allergy to mouse proteins
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- See Disease Characteristics
Endocrine therapy:
- Not specified
Radiotherapy:
- See Disease Characteristics
Surgery:
- See Disease Characteristics
Locations and Contacts
Memorial Sloan-Kettering Cancer Center, New York, New York 10021, United States
Additional Information
Clinical trial summary from the National Cancer Institute's PDQ® database
Starting date: August 1999
Last updated: May 23, 2008
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