Biological Therapy in Treating Patients With Neuroblastoma That Has Not Responded to Previous Treatment - Full Text View

Sponsor:	Memorial Sloan-Kettering Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00089258

Purpose

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	Intervention	Phase
Neuroblastoma	Biological: beta-glucan Biological: monoclonal antibody 3F8 Biological: sargramostim Drug: isotretinoin	Phase II

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Study of Anti-GD2 3F8 Antibody and Biologic Response Modifiers for High-Risk Neuroblastoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Neuroblastoma

Drug Information available for: Sargramostim Immunoglobulins Isotretinoin Globulin, Immune beta-Glucan

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Disease response as assessed by PT-PC at the end of 4 courses [ Designated as safety issue: No ]

Estimated Enrollment:	74
Study Start Date:	July 2004
Primary Completion Date:	November 2006 (Final data collection date for primary outcome measure)

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.

Eligibility

Genders Eligible for Study:	Both
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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089258

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

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000378186, MSKCC-04050
Study First Received:	August 4, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00089258 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Additional relevant MeSH terms:

Neuroectodermal Tumors, Primitive
Neoplasms by Histologic Type
Immunologic Factors
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Pharmacologic Actions
Neuroblastoma
Antibodies, Monoclonal
Neuroectodermal Tumors

Neoplasms
Antibodies
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Isotretinoin
Neoplasms, Neuroepithelial
Dermatologic Agents
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on November 22, 2009