Clinical trial NCT00492167: Beta-Glucan and Monoclonal Antibody 3F8 in Treating Patients With Metastatic Neuroblastoma
Official title: Phase I Study of Oral Yeast β-Glucan and Intravenous Anti-GD2 Monoclonal Antibody 3F8 Among Patients With Metastatic Neuroblastoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neuroblastoma
Keywords: recurrent neuroblastoma
regional neuroblastoma
stage 4S neuroblastoma
disseminated neuroblastoma
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-06-27
Enrollment: 45
Sex: ALL
Minimum age (years): 0
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Beta-glucan may stimulate the immune system and stop tumor cells from growing. Monoclonal antibodies, such as 3F8, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving beta-glucan together with monoclonal antibody 3F8 may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of beta-glucan when given together with monoclonal antibody 3F8 in treating patients with metastatic neuroblastoma.

Detailed description: OBJECTIVES:

Primary

* Determine the clinical toxicity of beta-glucan in combination with monoclonal antibody 3F8 in patients with metastatic neuroblastoma.
* Evaluate the biologic effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study of beta-glucan.

Patients receive oral beta-glucan once daily on days -4 to 12 and monoclonal antibody 3F8 IV over 30-90 minutes on days 1-5 and 8-12. Treatment repeats every 4 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity and with a human antimouse antibody (HAMA) titer \< 1,000 U/mL.

Cohorts of 3-6 patients receive escalating doses of beta-glucan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients undergo urine, bone marrow, and blood sample collection periodically for biological studies. Samples are analyzed for antibody-dependent cellular cytotoxicity, complement-mediated cytotoxicity, and serum HAMA response via immunohistochemistry.

After completion of study treatment, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of neuroblastoma by 1 of the following methods:

  * Histopathology
  * Bone marrow involvement AND elevated urinary catecholamines
* High-risk disease, defined by 1 of the following:

  * Stage 4 disease with MYCN amplification (any age) or without MYCN amplification (\> 18 months of age)
  * MYCN-amplified stage 3 disease (unresectable and any age)
  * MYCN-amplified stage 4S disease
* Metastatic disease
* Tumor progression or persistent disease (at metastatic or primary site) after intensive conventional chemotherapy
* Must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT scan or MRI) disease documented after completion of prior systemic therapy

PATIENT CHARACTERISTICS:

* Platelet count \> 25,000/mm\^3
* ANC \> 500/mm\^3
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No history of allergy to mouse proteins, beta-glucan, mushrooms, or yeast
* No active life-threatening infections
* No severe major organ toxicity

  * Concurrent toxicity must be ≤ grade 2 except for the following, which may be grade 3:

    * Myelosuppression
    * Hearing loss
    * Alopecia
    * Anorexia
    * Nausea
    * Hyperbilirubinemia from TPN
    * Anxiety
    * Hypomagnesemia
* No prior HAMA titer \> 1,000 U/mL by ELISA

PRIOR CONCURRENT THERAPY:

* No concurrent supplemental beta-glucan in food (e.g., bran cereals or mushrooms) or as complementary medicine
* No other concurrent systemic anticancer medications (e.g., hormonal agents, chemotherapy, investigational agents, or immunotherapy)

  * Concurrent isotretinoin allowed after the second course of study treatment is completed or if the patient develops human antimouse antibody (HAMA)

Primary outcomes:
measure: Toxicity
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Shakeel Modak, MD
role: STUDY_CHAIR
affiliation: Memorial Sloan Kettering Cancer Center
name: Brian H. Kushner, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cardenas FI, Mauguen A, Cheung IY, Kramer K, Kushner BH, Ragupathi G, Cheung NV, Modak S. Phase I Trial of Oral Yeast-Derived beta-Glucan to Enhance Anti-GD2 Immunotherapy of Resistant High-Risk Neuroblastoma. Cancers (Basel). 2021 Dec 14;13(24):6265. doi: 10.3390/cancers13246265.