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Induction Therapy Including 131 I-MIBG and Chemotherapy in Treating Patients With Newly Diagnosed High-Risk Neuroblastoma Undergoing Stem Cell Transplant, Radiation Therapy, and Maintenance Therapy With Isotretinoin

Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
No phase specifiedBiomarker/Laboratory analysis, TreatmentActive1 to 30NCI, OtherANBL09P1
NCI-2011-01745, CDR0000682629, U10CA098543, COG-ANBL09P1, NCT01175356

Trial Description

Summary

This clinical trial is studying induction therapy followed by iobenguane I 131 and chemotherapy in treating patients with newly diagnosed high-risk neuroblastoma undergoing stem cell transplant, radiation therapy, and maintenance therapy with isotretinoin. Radioisotope therapy, such as iobenguane I 131, releases radiation that kills tumor cells. Drugs used in chemotherapy, such as carboplatin, etoposide, busulfan, and melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. A peripheral stem cell transplant may be able to replace blood-forming cells that are destroyed by iobenguane I 131 and chemotherapy.

Further Study Information

PRIMARY OBJECTIVE:

I. To assess the feasibility of treating high-risk neuroblastoma patients, age 365 days to 30 years, with an induction block of meta-iodobenzylguanidine labeled with iodine-131 (131I-MIBG [iobenguane I 131])/irinotecan/vincristine delivered after multi-agent chemotherapy, and post-Induction busulfan/melphalan (Bu/Mel) consolidation therapy.

SECONDARY OBJECTIVES:

I. To assess the tolerability of these regimens in these patients, age 365 days - 30 years, with a) an Induction block of 131I-MIBG therapy delivered after multi-agent chemotherapy, and b) the tolerability of receiving post-Induction Bu/Mel Consolidation therapy with autologous stem-cell rescue (ASCR), and local radiation therapy.

TERTIARY OBJECTIVES:

I. To assess the response rate after a regimen of Induction chemotherapy and 131I-MIBG and after a consolidation regimen of Bu/Mel with ASCR and local radiation therapy.

II. To describe the relationship of tumor norepinephrine transporter (hNET) expression with radioiodinated MIBG uptake, at diagnosis as well as with tumor response.

III. To assess the relative reliability of 123 I-MIBG and 18FDG-PET imaging in assessment of tumor activity at diagnosis, and prior to surgical resection.

IV. To compare detectable tumor burden on the pre-surgical resection radioiodinated -MIBG diagnostic scan and the immediate post-MIBG therapy 131I-MIBG scan.

V. To test for the relationship of occurrence of sinusoidal obstruction syndrome (SOS) to Bu/Mel or to whole-body radiation dose or delayed radiation clearance due to 131I-MIBG.

VI. To analyze busulfan pharmacokinetics as measured by area under the curve (AUC) and to relate exposure to SOS incidence.

OUTLINE: This is a pilot, multicenter study.

INDUCTION CHEMOTHERAPY: Patients receive 5 courses of induction therapy.

Courses 1-2: Patients receive cyclophosphamide intravenously (IV) over 15-30 minutes and topotecan hydrochloride IV over 30 minutes on days 1-5. Patients undergo peripheral blood stem cell (PBSC) collection after course 2.

Course 3 and 5: Patients receive cisplatin IV over 1 hour on days 1-4 and etoposide phosphate IV over 1-2 hours on days 1-3. Patients undergo surgery to remove remaining tumor following course 5.

Course 4: Patients receive cyclophosphamide IV over 1-6 hours on days 1-2 and vincristine sulfate IV over 1 minute and doxorubicin hydrochloride IV over 24 hours on days 1-3.

Treatment repeats every 21 days for a total of 5 courses in the absence of disease progression or unacceptable toxicity. Patients without progressive disease proceed to iobenguane I 131 induction therapy beginning 3-6 weeks after course 5. Patients receive vincristine IV on day 0, irinotecan IV over 90 minutes on day 0-4, and iobenguane I 131 IV over 90-120 minutes on day 1.

SURGERY: Patients undergo surgery after course 4 or before consolidation therapy.

CONSOLIDATION THERAPY: Within 4-6 weeks after completion of induction therapy, patients receive busulfan IV over 2 hours every 6 hours on days -6 to -3 and melphalan IV on day -1. Patients also complete a questionnaire regarding costs for travel and accommodations during therapy. Blood samples maybe collected after the first dose of busulfan for pharmacokinetic assays.

AUTOLOGOUS STEM CELL RESCUE: Patients undergo infusion of PBSC on day 0.

RADIOTHERAPY: Beginning no sooner than 42 days after peripheral blood stem cell infusion, patients undergo 12 fractions of external-beam radiotherapy (2D, 3D-conformal, or intensity-modulated) to all areas of residual disease, primary tumor site, and involved nodal disease.

MAINTENANCE THERAPY: Beginning 66 days after transplantation, patients receive isotretinoin orally (PO) twice daily (BID) on days 1-14. Treatment repeats every 28 days for 6 courses.

After completion of study therapy, patients are followed up every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.

Eligibility Criteria

Inclusion Criteria:

  • Patients have a diagnosis of neuroblastoma (ICD-O morphology 9500/3) or ganglioneuroblastoma verified by histology or demonstration of clumps of tumor cells in bone marrow with elevated urinary catecholamine metabolites; patients with the following disease stages at diagnosis are eligible, if they meet the other specified criteria:
  • Patients with newly diagnosed neuroblastoma with INSS Stage 4 are eligible with the following:
  • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days regardless of additional biologic features
  • Age > 18 months (> 547 days) regardless of biologic features
  • Age 12-18 months (365-547 days) with any of the following 3 unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index = 1) or any biologic feature that is indeterminant/unsatisfactory/unknown
  • Patients with newly diagnosed neuroblastoma with INSS Stage 3 are eligible with the following:
  • MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals), and age >= 365 days, regardless of additional biologic features
  • Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
  • Patients with newly diagnosed INSS Stage 2a/2b with MYCN amplification (> 4-fold increase in MYCN signals as compared to reference signals) and age >= 365 days, regardless of additional biologic features
  • Patients >= 365 days initially diagnosed with: INSS Stage 1, 2, 4S who progressed to a Stage 4 without interval chemotherapy; these patients must have been enrolled on ANBL00B1; it is to be noted that study enrollment must occur within 4 weeks of progression to Stage 4 for INSS Stage 1, 2, 4S
  • Patients must have had no prior systemic therapy except for localized emergency radiation to sites of life- threatening or function-threatening disease and/or no more than 1 cycle of chemotherapy per Low- or Intermediate-Risk neuroblastoma therapy (P9641, A3961, ANBL0531) prior to determination of MYCN amplification and histology
  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73m^2 OR serum creatinine based on age and/or gender as follows:
  • =< 0.6 mg/dL (1 to < 2 years of age)
  • =< 0.8 mg/dL (2 to < 6 years of age)
  • =< 1.0 mg/dL (6 to < 10 years of age)
  • =< 1.2 mg/dL (10 to < 13 years of age)
  • =< 1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)
  • =< 1.7 mg/dL (male) or 1.4 mg/dL (female) ( >= 16 years of age)
  • Total bilirubin =< 1.5 times upper limit of normal (ULN) for age
  • Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 times ULN for age
  • Shortening fraction >= 27% by echocardiogram (ECHO) or
  • Ejection fraction >= 50% by radionuclide evaluation
  • No known contraindication to peripheral blood stem cell (PBSC) collection; examples of contraindications might be a weight or size less than the collecting institution finds feasible, or a physical condition that would limit the ability of the child to undergo apheresis catheter placement (if necessary) and/or the apheresis procedure
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Females of childbearing potential must have a negative pregnancy test; patients of childbearing potential must agree to use an effective birth control method
  • Female patients who are lactating must agree to stop breast-feeding
  • Patients that are 12-18 months of age with INSS Stage 4 and all 3 favorable biologic features (i.e., non-amplified MYCN, favorable pathology, and DNA index > 1) are not eligible
  • Patients are not eligible if they have received local radiation which includes any of the following: 1200 cGy to more than 33% of both kidneys (patient must have at least 1 kidney that has not exceeded the dose/volume of radiation listed) or 1800 cGy to more than 30% of liver and/or 900 cGy to more than 50% of liver; emergency local irradiation is allowed prior to study entry, provided the patient still meets eligibility criteria

Trial Contact Information

Trial Lead Organizations/Sponsors

Children's Oncology Group

National Cancer Institute

Brian Weiss, MDPrincipal Investigator

Trial Sites

U.S.A.
Alabama
  Birmingham
 Children's Hospital of Alabama at University of Alabama at Birmingham
 Alyssa T Reddy Ph: 205-934-0309
 UAB Comprehensive Cancer Center
 Alyssa T Reddy Ph: 205-934-0309
Arizona
  Phoenix
 Phoenix Children's Hospital
 Jessica Boklan Ph: 602-546-0920
California
  Los Angeles
 Children's Hospital Los Angeles
 Leo Mascarenhas Ph: 323-361-4110
  San Francisco
 UCSF Helen Diller Family Comprehensive Cancer Center
 Katherine K Matthay Ph: 877-827-3222
Colorado
  Aurora
 Children's Hospital Colorado Center for Cancer and Blood Disorders
 Timothy P Garrington Ph: 720-777-6672
Connecticut
  Hartford
 Connecticut Children's Medical Center
 Michael S Isakoff Ph: 860-545-9981
District of Columbia
  Washington
 Children's National Medical Center
 Jeffrey S Dome Ph: 202-884-2549
Illinois
  Chicago
 University of Chicago Cancer Research Center
 Susan L Cohn Ph: 773-834-7424
Massachusetts
  Boston
 Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
 Carlos Rodriguez-Galindo Ph: 866-790-4500
North Carolina
  Chapel Hill
 Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
 Stuart H Gold Ph: 877-668-0683
  Email: cancerclinicaltrials@med.unc.edu
  Durham
 Duke Cancer Institute
 Susan G Kreissman Ph: 888-275-3853
Ohio
  Cincinnati
 Cincinnati Children's Hospital Medical Center
 Brian D Weiss Ph: 513-636-2799
Pennsylvania
  Philadelphia
 Children's Hospital of Philadelphia
 Yael P. Mosse Ph: 215-590-2810
South Carolina
  Charleston
 Hollings Cancer Center at Medical University of South Carolina
 Jacqueline M Kraveka Ph: 843-792-9321
Texas
  Dallas
 Simmons Comprehensive Cancer Center at University of Texas Southwestern Medical Center - Dallas
 Naomi J Winick Ph: 214-648-7097
  Fort Worth
 Cook Children's Medical Center - Fort Worth
 Mary Meaghan P Granger Ph: 682-885-2103
Utah
  Salt Lake City
 Primary Children's Medical Center
 Phillip E Barnette Ph: 801-585-5270
Washington
  Seattle
 Children's Hospital and Regional Medical Center - Seattle
 Douglas S Hawkins Ph: 866-987-2000
  Spokane
 Providence Cancer Center at Sacred Heart Medical Center
 Judy L Felgenhauer Ph: 800-228-6618
  Email: HopeBeginsHere@providence.org
Wisconsin
  Madison
 University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
 Kenneth B DeSantes Ph: 608-262-5223
  Milwaukee
 Midwest Children's Cancer Center at Children's Hospital of Wisconsin
 Meghen B Browning Ph: 414-805-4380

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01175356
ClinicalTrials.gov processed this data on March 03, 2014

Note: Information about this trial is from the ClinicalTrials.gov database. The versions designated for health professionals and patients contain the same text. Minor changes may be made to the ClinicalTrials.gov record to standardize the names of study sponsors, sites, and contacts. Cancer.gov only lists sites that are recruiting patients for active trials, whereas ClinicalTrials.gov lists all sites for all trials. Questions and comments regarding the presented information should be directed to ClinicalTrials.gov.

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