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Monoclonal Antibody Therapy Plus Etoposide in Treating Patients With Neuroblastoma

Primary Purpose

Neuroblastoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
monoclonal antibody 3F8
etoposide
isotretinoin
Sponsored by
Memorial Sloan Kettering Cancer Center
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring regional neuroblastoma, disseminated neuroblastoma, recurrent neuroblastoma, localized unresectable neuroblastoma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Memorial Sloan-Kettering Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
December 10, 1999
Last Updated
October 30, 2013
Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00004110
Brief Title
Monoclonal Antibody Therapy Plus Etoposide in Treating Patients With Neuroblastoma
Official Title
Monoclonal Antibody 3F8 and Oral Etoposide for the Treatment of Neuroblastoma
Study Type
Interventional

2. Study Status

Record Verification Date
October 2013
Overall Recruitment Status
Completed
Study Start Date
August 1999 (undefined)
Primary Completion Date
September 2004 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Memorial Sloan Kettering Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neuroblastoma
Keywords
regional neuroblastoma, disseminated neuroblastoma, recurrent neuroblastoma, localized unresectable neuroblastoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Masking
None (Open Label)

8. Arms, Groups, and Interventions

Intervention Type
Biological
Intervention Name(s)
monoclonal antibody 3F8
Intervention Type
Drug
Intervention Name(s)
etoposide
Intervention Type
Drug
Intervention Name(s)
isotretinoin

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nai-Kong V. Cheung, MD, PhD
Organizational Affiliation
Memorial Sloan Kettering Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States

12. IPD Sharing Statement

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Monoclonal Antibody Therapy Plus Etoposide in Treating Patients With Neuroblastoma

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