N2004-06: Irinotecan and Vincristine With 131I-MIBG Therapy for Resistant/Relapsed High-Risk Neuroblastoma

NCT00509353 | Completed Phase 1 DMC FDA Drug

• 4 other identifiers: CDR0000558042P01CA081403N2004-06NANT-Draximage-2007-01
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 12

Brief Summary

RATIONALE: Radioactive drugs, such as iodine I 131 metaiodobenzylguanidine (MIGB), may carry radiation directly to tumor cells and not harm normal cells. Drugs used in chemotherapy, such as irinotecan and vincristine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving iodine I 131 MIGB together with irinotecan and vincristine may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of iodine I 131 MIGB when given together with irinotecan and vincristine in treating young patients with resistant or relapsed high-risk neuroblastoma.

Conditions

Neuroblastoma

Keywords

recurrent neuroblastoma

Outcome Measures

Primary Outcomes (2)

• To determine the maximum tolerated dose (MTD) of 131I-MIBG given in combination with fixed-dose irinotecan/vincristine to children with high-risk refractory/relapsed neuroblastoma.

  Tolerability will be assessed throughout the study.

• To determine the dose limiting toxicities of 131I-MIBG combined with irinotecan/vincristine.

  Adverse events, clinically significant changes in laboratory results, and vital signs, to be measured throughout the study.

Secondary Outcomes (1)

• Within the confines of a Phase I study, to determine if there is a therapeutic response to this regimen.

  Disease response will be evaluated at baseline, prior to each cycle and at the end of treatment.

Study Arms (1)

Single Group

EXPERIMENTAL

Drug: irinotecan hydrochloride; Drug: vincristine sulfate; Radiation: iobenguane I 131

Interventions

irinotecan hydrochloride DRUG

Single Group

vincristine sulfate DRUG

Single Group

iobenguane I 131 RADIATION

Single Group

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Must have a diagnosis of neuroblastoma by histologic verification and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines
• Must have high-risk neuroblastoma AND meets at least one of the following criteria:
• Recurrent or progressive disease at any time
• Biopsy not required, even if there is partial response to intervening therapy
• Refractory disease (i.e., less than a partial response to frontline therapy, including a minimum of 4 courses of chemotherapy)
• Biopsy not required
• If the patient has not had previous myeloablative therapy, preference will be given to NANT-2001-02 (iodine I 131 metaiodobenzylguanidine \[\^131I-MIBG\] + CEM)
• Persistent disease after at least a partial response to frontline therapy (i.e., patient still has residual disease by MIBG scan, CT/MRI scan, or bone marrow)
• Biopsy required (bone marrow biopsy included) of at least one residual site demonstrating viable neuroblastoma
• If the patient has not had previous myeloablative therapy, preference will be given to NANT-2001-02 (\^131I-MIBG + CEM)
• Must have evidence of MIBG uptake into tumor at ≥ 1 site within 4 weeks prior to study entry and subsequent to any intervening therapy
• Must have autologous hematopoietic stem cell product available and it must be free of tumor cell contamination (0 tumor cells /1,000,000 nucleated cells), cryopreserved, and available for re-infusion after \^131I-MIBG treatment, if immunocytology has been performed on the stem cell product
• If immunocytology has not been performed on the stem cell product, then bilateral bone marrow aspirates and biopsies must have been negative by morphology within 4 weeks before or after the stem cell collection
• If the patient had no bone marrow disease documented at diagnosis or at any time prior to peripheral blood stem cell (PBSC) harvest then the criteria for bilateral bone marrow aspirates/biopsies is waived
• The minimum dose is as follows:

You may not qualify if:

• Pregnancy or breast feeding
• Dyspnea at rest, exercise intolerance, pleural effusion, or oxygen requirement
• Disease of any major organ system that would compromise the patient's ability to withstand therapy
• Documented allergy to third generation cephalosporins
• Active diarrhea (defined as ≥ grade 2 per CTCAE v3)
• Active or uncontrolled infection, including C. difficile
• Patients on prolonged antifungal therapy are eligible if suspected radiographic lesions are culture and biopsy negative and patient meets other organ function criteria
• Patients and/or families who are physically and psychologically unable to cooperate with the radiation safety isolation
• Patient weight that would require exceeding a maximum total allowable dose of \^131I-MIBG (per institutional guidelines)
• Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
• PRIOR CONCURRENT THERAPY:
• Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before study entry
• At least 3 weeks since prior myelosuppressive or biologic therapy
• At least 2 weeks since prior radiation therapy
• Radiation therapy should not be given to the only site of measurable or evaluable disease

Sponsors & Collaborators

• New Approaches to Neuroblastoma Therapy Consortium: lead
• National Cancer Institute (NCI): collaborator

Study Sites (12)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Packard Children's Hospital at Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

C.S. Mott Children's Hospital at University of Michigan Medical Center

Ann Arbor, Michigan, 48109-0286, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

University of Wisconsin Paul P. Carbone Comprehensive Cancer Center

Madison, Wisconsin, 53792-6164, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Irinotecan; Vincristine; 3-Iodobenzylguanidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated

Study Officials

• Steven DuBois, MD

  UCSF Medical Center at Parnassus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2007
• First Posted: July 31, 2007
• Study Start: January 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: May 1, 2012
• Last Updated: April 14, 2026

Record last verified: 2023-11

Locations

US (12)