Biological Therapy in Treating Patients With Neuroblastoma That Has Not Responded to Previous Treatment

• ClinicalTrials.gov Identifier: NCT00089258
• Recruitment Status: Completed
• First Posted: August 5, 2004
• Last Update Posted: January 17, 2013
• Sponsor: Memorial Sloan Kettering Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Information provided by: Memorial Sloan Kettering Cancer Center

Study Description

Brief Summary:

RATIONALE: Monoclonal antibodies, such as monoclonal antibody 3F8, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Beta-glucan, isotretinoin, and sargramostim may increase the effectiveness of monoclonal antibody 3F8 by making tumor cells more sensitive to the monoclonal antibody. Combining different types of biological therapy may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving beta-glucan, isotretinoin, and sargramostim together with monoclonal antibody 3F8 works in treating patients with neuroblastoma that has not responded to previous treatment.

Condition or disease	Intervention/treatment	Phase
Neuroblastoma	Biological: beta-glucan; Biological: monoclonal antibody 3F8; Biological: sargramostim; Drug: isotretinoin	Phase 2

Detailed Description:

OBJECTIVES:

• Determine the efficacy of beta-glucan, isotretinoin, and sargramostim (GM-CSF) in enhancing monoclonal antibody 3F8-mediated ablation in patients with high-risk refractory neuroblastoma.
• Determine the antitumor activity of this regimen, in terms of assessing disease status in the bone marrow by real-time quantitative reverse transcription polymerase chain reaction, in these patients.
• Determine the toxicity of this regimen in these patients.

OUTLINE: This is an open-label study. Patients are stratified according to refractory disease (primary refractory [never had disease progression or disease recurrence] vs secondary refractory [recurrent disease that did not respond completely to reinduction therapy]).

• Courses 1 and 2: Patients receive sargramostim (GM-CSF) subcutaneously once daily on days -5 to 11. Patients also receive oral beta-glucan once daily on days -2 to 11 and monoclonal antibody (MOAB) 3F8 IV over 30-90 minutes on days 0-4 and 7-11.
• Courses 3 and 4: Patients receive GM-CSF, beta-glucan, and MOAB 3F8 as above. Patients also receive oral isotretinoin twice daily on days -2 to 11.

Treatment repeats every 2-4 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years.

PROJECTED ACCRUAL: A total of 27-74 patients (10-33 for stratum 1 and 17-41 for stratum 2) will be accrued for this study.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 74 participants
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Anti-GD2 3F8 Antibody and Biologic Response Modifiers for High-risk Neuroblastoma
• Study Start Date: July 2004
• Actual Primary Completion Date: November 2006

Arms and Interventions

Outcome Measures

Primary Outcome Measures :

1. Disease response as assessed by PT-PC at the end of 4 courses

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of neuroblastoma, as defined by 1 of the following:

  • Histologically confirmed disease
  • Bone marrow metastases plus high urine catecholamines

• High-risk disease meeting 1 of the following stage criteria:

  • Stage IV, with 1 of the following:

    • Any age with MYCN amplification
    • > 18 months of age without MYCN amplification

  • Stage III, with both of the following:

    • Any age with MYCN amplification
    • Unresectable disease
  • Stage 4S with MYCN amplification
• Measurable or evaluable soft tissue disease
• Relapsed disease resistant to standard induction chemotherapy and salvage therapy

PATIENT CHARACTERISTICS:

Age

• Any age

Performance status

• Not specified

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• No severe hepatic toxicity ≥ grade 3

Renal

• No severe renal toxicity ≥ grade 3

Cardiovascular

• No severe cardiac toxicity ≥ grade 3

Pulmonary

• No severe pulmonary toxicity ≥ grade 3

Other

• Not pregnant
• Negative pregnancy test
• No severe neurologic toxicity ≥ grade 3
• No severe gastrointestinal toxicity ≥ grade 3
• No other severe major organ dysfunction except ototoxicity
• No history of allergy to mouse proteins
• No active life-threatening infection
• No human anti-mouse antibody titer > 1,000 ELISA units/mL

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Contacts and Locations

Locations

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10021

Sponsors and Collaborators

Memorial Sloan Kettering Cancer Center

National Cancer Institute (NCI)

Investigators

• Study Chair: Nai-Kong V. Cheung, MD, PhD; Memorial Sloan Kettering Cancer Center

More Information

• ClinicalTrials.gov Identifier: NCT00089258
• Other Study ID Numbers: 04-050; MSKCC-04050
• First Posted: August 5, 2004
• Last Update Posted: January 17, 2013
• Last Verified: January 2013

Keywords provided by Memorial Sloan Kettering Cancer Center:

localized unresectable neuroblastoma; disseminated neuroblastoma; regional neuroblastoma; stage 4S neuroblastoma; recurrent neuroblastoma

Additional relevant MeSH terms:

Neuroblastoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Isotretinoin; Antibodies; Antibodies, Monoclonal; Sargramostim; Immunologic Factors; Physiological Effects of Drugs; Dermatologic Agents