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Irinotecan Hydrochloride and Temozolomide with Temsirolimus or Dinutuximab in Treating Younger Patients with Refractory or Relapsed Neuroblastoma

Trial Status: Closed to Accrual and Intervention

This randomized phase II trial studies how well irinotecan hydrochloride and temozolomide with temsirolimus or dinutuximab work in treating younger patients with neuroblastoma that has returned or does not respond to treatment. Drugs used in chemotherapy, such as irinotecan hydrochloride and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Temsirolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as dinutuximab, may find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether giving irinotecan hydrochloride and temozolomide together with temsirolimus or dinutuximab is more effective in treating neuroblastoma.

Inclusion Criteria

  • Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e., > 2 x upper limit of normal [ULN]), at the time of initial diagnosis
  • For the purposes of this study, aggressive multidrug chemotherapy is defined as chemotherapy including 2 or more agents that must include an alkylating agent and a platinum-containing compound; patients must have ONE of the following: * First episode of recurrent disease following completion of aggressive multi-drug frontline therapy * First episode of progressive disease during aggressive multi-drug frontline therapy * Primary resistant/refractory disease (less than partial response by INRC) detected at the conclusion of at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (examples include A3973, ANBL0532, ANBL09P1, etc.)
  • Patients must have at least ONE of the following: * Measurable tumor on magnetic resonance imaging (MRI), computed tomography (CT) scan obtained within 3 weeks prior to study entry; measurable is defined as >= 10 mm in at least one dimension on spiral/helical CT that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased fludeoxyglucose (FDG) uptake on positron emission tomography (PET) scan * MIBG scan obtained within 3 weeks prior to study entry with positive uptake at a minimum of one site; this site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction * Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma; biopsy is not required for patients who have new site of soft tissue disease (radiographic evidence of disease progression) regardless of whether progression occurs while receiving therapy or after completion of therapy * Note: Patients with elevated catecholamines (i.e., > 2 x ULN) only or bone marrow disease only are NOT eligible for this study
  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age
  • Patients must have received frontline therapy (including surgery, chemotherapy, autologous stem cell transplant [SCT] +/- MIBG, immunotherapy, radiotherapy, and retinoids) but may NOT have received second line chemotherapy for resistant/refractory, relapsed disease or progressive disease
  • At least 14 days must have elapsed since completion of myelosuppressive therapy
  • At least 7 days must have elapsed since the completion of therapy with a non-myelosuppressive biologic agent or retinoid
  • No interim time prior to study entry is required following prior radiation therapy (RT) for non-target lesions; however, patients must not have received radiation for a minimum of 4 weeks prior to study entry at the site of any lesion that will be identified as a target lesion to measure tumor response; lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma; palliative radiation is allowed to sites that will not be used to measure response during this study
  • Patients are eligible >= 6 weeks after autologous stem cell transplants or stem cell infusions as long as hematologic and other eligibility criteria have been met
  • Patients are eligible >= 6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met
  • Subjects who have previously received anti-GD2 monoclonal antibodies for biologic therapy or for tumor imaging are eligible unless they have had progressive disease while receiving prior anti-GD2 therapy; subjects who have received autologous marrow infusions or autologous stem cell infusions that were purged using monoclonal antibody linked to beads, but no other form of anti-GD2 monoclonal antibody, are eligible
  • Patients must not have received long-acting myeloid growth factors (e.g., Neulasta) within 14 days of entry on this study; seven days must have elapsed since administration of a short acting myeloid growth factor
  • Peripheral absolute neutrophil count (ANC) >= 750/uL
  • Platelet count >= 75,000/uL (transfusion independent)
  • Patients known to have bone marrow involvement with neuroblastoma are eligible provided that minimum ANC and platelet count criteria are met but are not evaluable for hematological toxicity
  • Creatinine clearance or estimated radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or
  • A serum creatinine =< upper limit of normal (ULN) based on age/gender as follows: * Age 1 month to < 6 months: 0.4 for males, 0.4 for females * Age 6 months to < 1 year: 0.5 for males, 0.5 for females * Age 1 to < 2 years: 0.6 for males, 0.6 for females * Age 2 to < 6 years: 0.8 for males, 0.8 for females * Age 6 to < 10 years: 1 for males, 1 for females * Age 10 to < 13 years: 1.2 for males, 1.2 for females * Age 13 to < 16 years: 1.5 for males, 1.4 for females * Age >= 16 years: 1.7 for males, 1.4 for females
  • Total bilirubin =< 1.5 x ULN for age AND
  • Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5.0 x ULN for age (=< 225 U/L); for the purpose of this study, the ULN for SGPT is 45 U/L
  • Adequate central nervous system function defined as: * Patients with a history of central nervous system (CNS) disease must have no clinical or radiological evidence of CNS disease at the time of study enrollment * Patients with seizure disorders may be enrolled if seizures are well controlled on anticonvulsants * CNS toxicity =< grade 2
  • Shortening fraction of >= 27% by echocardiogram (ECHO) OR
  • Ejection fraction >= 50% by ECHO or gated radionuclide study
  • Adequate coagulation defined as: * Prothrombin time (PT) =< 1.2 x upper limit of normal
  • Adequate pulmonary function defined as: * No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry > 94% if there is a clinical indication for pulse oximetry; normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung of carbon monoxide [DLCO]) are required if there is a clinical indication for determination; for patients who do not have respiratory symptoms, full pulmonary function tests (PFTs) are NOT required

Exclusion Criteria

  • Men and women of childbearing potential and their partners must agree to use adequate contraception while enrolled on this study; based on the established teratogenic potential of alkylating agents, pregnant women will be excluded from this study; female patients who are lactating must agree to stop breastfeeding or will otherwise be excluded from this study; females of childbearing potential must have a negative pregnancy test to be eligible for this study
  • Patients with elevated catecholamines (i.e., > 2 x ULN) only or bone marrow disease only are NOT eligible for this study
  • Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment; patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible; the only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions; the use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency
  • Patients must not have received enzyme-inducing anticonvulsants including phenytoin, phenobarbital, valproic acid, or carbamazepine for at least 7 days prior to study enrollment; patients receiving non-enzyme inducing anticonvulsants such as gabapentin or levetiracetam will be eligible
  • Patients must not have been diagnosed with myelodysplastic syndrome or with any malignancy other than neuroblastoma
  • Patients with symptoms of congestive heart failure are not eligible
  • Patients must not have >= grade 2 diarrhea
  • Patients must not have uncontrolled infection
  • Patients with a history of grade 4 allergic reactions to anti-GD2 antibodies or reactions that required discontinuation of the anti-GD2 therapy are not eligible
  • Patients with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible

Arizona

Phoenix
Phoenix Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Jessica Boklan
Phone: 602-546-0920

Arkansas

Little Rock
Arkansas Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: David L. Becton
Phone: 501-686-8274
University of Arkansas for Medical Sciences
Status: CLOSED_TO_ACCRUAL
Contact: David L. Becton
Phone: 501-686-8274

California

Downey
Kaiser Permanente Downey Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Robert Michael Cooper
Phone: 626-564-3455
Loma Linda
Loma Linda University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Albert Kheradpour
Phone: 909-558-3375
Los Angeles
Children's Hospital Los Angeles
Status: CLOSED_TO_ACCRUAL
Contact: Leo Mascarenhas
Madera
Valley Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Vonda Lee Crouse
Oakland
Kaiser Permanente-Oakland
Status: CLOSED_TO_ACCRUAL
Contact: Steven K. Bergstrom
Phone: 510-891-3400
Orange
Children's Hospital of Orange County
Status: CLOSED_TO_ACCRUAL
Contact: Elyssa M. Rubin
Palo Alto
Lucile Packard Children's Hospital Stanford University
Status: CLOSED_TO_ACCRUAL
Contact: Sheri L. Spunt
Phone: 650-498-7061
Sacramento
Sutter Medical Center Sacramento
Status: CLOSED_TO_ACCRUAL
Contact: Yung Soon Yim
Phone: 415-209-2686
University of California Davis Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Marcio Henrique Malogolowkin
Phone: 916-734-3089
San Diego
Rady Children's Hospital - San Diego
Status: CLOSED_TO_ACCRUAL
Contact: William D. Roberts
San Francisco
UCSF Medical Center-Mission Bay
Status: CLOSED_TO_ACCRUAL
Contact: Katherine Kurshan Matthay
Phone: 877-827-3222
UCSF Medical Center-Parnassus
Status: CLOSED_TO_ACCRUAL
Contact: Katherine Kurshan Matthay
Phone: 877-827-3222

Colorado

Aurora
Children's Hospital Colorado
Status: CLOSED_TO_ACCRUAL
Contact: Margaret Ellen Macy
Denver
Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Jennifer Jocelyn Clark

Connecticut

Hartford
Connecticut Children's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Michael Scott Isakoff
Phone: 800-579-7822
New Haven
Yale University
Status: CLOSED_TO_ACCRUAL
Contact: Nina Singh Kadan-Lottick
Phone: 203-785-5702

Delaware

Wilmington
Alfred I duPont Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian

District of Columbia

Washington
Children's National Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Jeffrey Stuart Dome
MedStar Georgetown University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Aziza Tahir Shad
Phone: 410-601-6120

Florida

Fort Myers
Golisano Children's Hospital of Southwest Florida
Status: CLOSED_TO_ACCRUAL
Contact: Emad K. Salman
Phone: 877-680-0008
Lee Memorial Health System
Status: CLOSED_TO_ACCRUAL
Contact: Emad K. Salman
Phone: 877-680-0008
Gainesville
University of Florida Health Science Center - Gainesville
Status: CLOSED_TO_ACCRUAL
Contact: William Birdsall Slayton
Hollywood
Memorial Regional Hospital / Joe DiMaggio Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Iftikhar Hanif
Jacksonville
Nemours Children's Clinic-Jacksonville
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Miami
Nicklaus Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Enrique Alberto Escalon
University of Miami Miller School of Medicine-Sylvester Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Julio Cesar Barredo
Phone: 305-243-2647
Orlando
AdventHealth Orlando
Status: CLOSED_TO_ACCRUAL
Contact: Fouad M. Hajjar
Phone: 407-303-2090
Nemours Children's Clinic - Orlando
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Phone: 888-823-5923
Nemours Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Pensacola
Nemours Children's Clinic - Pensacola
Status: CLOSED_TO_ACCRUAL
Contact: Ramamoorthy Nagasubramanian
Saint Petersburg
Johns Hopkins All Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Nanette H. Grana
Tampa
Saint Joseph's Hospital / Children's Hospital-Tampa
Status: CLOSED_TO_ACCRUAL
Contact: Mark J. Mogul
West Palm Beach
Saint Mary's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Narayana Gowda

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: CLOSED_TO_ACCRUAL
Contact: Kelly C. Goldsmith
Savannah
Memorial Health University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: J. Martin Johnston
Phone: 912-350-8568

Hawaii

Honolulu
Kapiolani Medical Center for Women and Children
Status: CLOSED_TO_ACCRUAL
Contact: Wade T. Kyono
Phone: 808-586-2979
University of Hawaii Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Robert W. Wilkinson
Phone: 888-823-5923

Idaho

Boise
Saint Luke's Cancer Institute - Boise
Status: CLOSED_TO_ACCRUAL
Contact: Eugenia Chang

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: CLOSED_TO_ACCRUAL
Contact: Yasmin Castellanes Gosiengfiao
University of Chicago Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Susan Lerner Cohn
Phone: 773-834-7424
University of Illinois
Status: CLOSED_TO_ACCRUAL
Contact: Mary Lou Schmidt
Phone: 312-355-3046
Maywood
Loyola University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Eugene Suh
Phone: 708-226-4357
Oak Lawn
Advocate Children's Hospital-Oak Lawn
Status: CLOSED_TO_ACCRUAL
Contact: Rebecca Erin McFall
Peoria
Saint Jude Midwest Affiliate
Status: CLOSED_TO_ACCRUAL
Contact: Pedro A. De Alarcon
Phone: 888-226-4343
Springfield
Southern Illinois University School of Medicine
Status: CLOSED_TO_ACCRUAL
Contact: Gregory P. Brandt
Phone: 217-545-7929

Indiana

Indianapolis
Riley Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Sandeep Batra
Phone: 317-944-8784
Email: batras@iu.edu
Saint Vincent Hospital and Health Care Center
Status: CLOSED_TO_ACCRUAL
Contact: Bassem I. Razzouk
Phone: 317-338-2194

Iowa

Des Moines
Blank Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Wendy Leigh Woods-Swafford
Phone: 515-241-3305
Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Mariko Sato
Phone: 800-237-1225

Kentucky

Lexington
University of Kentucky / Markey Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Lars Martin Wagner
Phone: 859-257-3379
Louisville
Norton Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ashok B. Raj
Phone: 502-562-3429

Louisiana

New Orleans
Children's Hospital New Orleans
Status: CLOSED_TO_ACCRUAL
Contact: Lolie C. Yu
Ochsner Medical Center Jefferson
Status: CLOSED_TO_ACCRUAL
Contact: Craig Lotterman
Phone: 504-842-3708

Maine

Bangor
Eastern Maine Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Nadine Patricia Sauer SantaCruz
Phone: 207-973-4274

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Allen R. Chen
Phone: 510-891-3400
Sinai Hospital of Baltimore
Status: CLOSED_TO_ACCRUAL
Contact: Jason M. Fixler
Phone: 410-601-6120

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Suzanne Shusterman
Phone: 877-442-3324

Michigan

Ann Arbor
C S Mott Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Rajen Mody
Detroit
Ascension Saint John Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Adonis N. Lorenzana
Phone: 313-343-3166
Wayne State University / Karmanos Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Zhihong Joanne Wang
Phone: 313-576-9363
East Lansing
Michigan State University Clinical Center
Status: CLOSED_TO_ACCRUAL
Contact: Renuka Gera
Phone: 517-975-9547
Grand Rapids
Helen DeVos Children's Hospital at Spectrum Health
Status: CLOSED_TO_ACCRUAL
Contact: David Scott Dickens
Phone: 616-391-1230

Minnesota

Minneapolis
Children's Hospitals and Clinics of Minnesota - Minneapolis
Status: CLOSED_TO_ACCRUAL
Contact: Michael Kerr Richards
University of Minnesota / Masonic Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Emily G. Greengard
Rochester
Mayo Clinic in Rochester
Status: CLOSED_TO_ACCRUAL
Contact: Carola A. S. Arndt
Phone: 855-776-0015

Mississippi

Jackson
University of Mississippi Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Gail Cranshaw Megason
Phone: 601-815-6700

Missouri

Kansas City
Children's Mercy Hospitals and Clinics
Status: CLOSED_TO_ACCRUAL
Contact: Keith Jason August
Phone: 888-823-5923
Saint Louis
Mercy Hospital Saint Louis
Status: CLOSED_TO_ACCRUAL
Contact: Bethany Graham Sleckman
Phone: 800-600-3606
Washington University School of Medicine
Status: CLOSED_TO_ACCRUAL
Contact: Robert J. Hayashi
Phone: 800-600-3606

Nebraska

Omaha
Children's Hospital and Medical Center of Omaha
Status: CLOSED_TO_ACCRUAL
Contact: Minnie Abromowitch
University of Nebraska Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Minnie Abromowitch

Nevada

Las Vegas
Alliance for Childhood Diseases / Cure 4 the Kids Foundation
Status: CLOSED_TO_ACCRUAL
Contact: Alan K. Ikeda
Phone: 702-384-0013
Nevada Cancer Research Foundation NCORP
Status: ACTIVE
Contact: Jonathan Bernstein
Phone: 702-384-0013
Summerlin Hospital Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Alan K. Ikeda
Phone: 702-384-0013
Sunrise Hospital and Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Alan K. Ikeda
Phone: 702-384-0013
University Medical Center of Southern Nevada
Status: CLOSED_TO_ACCRUAL
Contact: Alan K. Ikeda
Phone: 702-384-0013

New Hampshire

Lebanon
Dartmouth Hitchcock Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Sara Chaffee
Phone: 800-639-6918

New Jersey

Hackensack
Hackensack University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Burton Eliot Appel
Phone: 201-996-2879
Morristown
Morristown Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Steven Lon Halpern
Phone: 201-996-2879
New Brunswick
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Richard A. Drachtman
Phone: 732-235-8675

New Mexico

Albuquerque
University of New Mexico Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Koh B. Boayue
Phone: 505-925-0366

New York

Albany
Albany Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Vikramjit Singh Kanwar
Phone: 518-262-3368
Bronx
Montefiore Medical Center - Moses Campus
Status: CLOSED_TO_ACCRUAL
Contact: Lisa Gennarini
Phone: 718-904-2730
Buffalo
Roswell Park Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Clare J. Twist
Phone: 650-498-7061
Mineola
NYU Winthrop Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Mark E. Weinblatt
Phone: 516-663-3115
New Hyde Park
The Steven and Alexandra Cohen Children's Medical Center of New York
Status: CLOSED_TO_ACCRUAL
Contact: Jonathan D. Fish
New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Alice Lee
Phone: 212-305-8615
Rochester
University of Rochester
Status: CLOSED_TO_ACCRUAL
Contact: Jeffrey Robert Andolina
Phone: 585-275-5830
Syracuse
State University of New York Upstate Medical University
Status: CLOSED_TO_ACCRUAL
Contact: Philip M. Monteleone
Phone: 315-464-5476
Valhalla
New York Medical College
Status: CLOSED_TO_ACCRUAL
Contact: Jessica Cassara Hochberg
Phone: 914-594-3794

North Carolina

Asheville
Mission Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Douglas James Scothorn
Phone: 828-213-4150
Chapel Hill
UNC Lineberger Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Stuart Harrison Gold
Phone: 877-668-0683
Charlotte
Carolinas Medical Center / Levine Cancer Institute
Status: CLOSED_TO_ACCRUAL
Contact: Joel A. Kaplan
Phone: 704-355-2884
Durham
Duke University Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Susan G. Kreissman
Phone: 888-275-3853

North Dakota

Fargo
Sanford Broadway Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Samuel Odame Anim
Phone: 800-437-4010

Ohio

Akron
Children's Hospital Medical Center of Akron
Status: CLOSED_TO_ACCRUAL
Contact: Steven J. Kuerbitz
Cincinnati
Cincinnati Children's Hospital Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Brian David Weiss
Cleveland
Rainbow Babies and Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Yousif (Joe) H. Matloub
Phone: 216-844-5437
Columbus
Nationwide Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Mark Anthony Ranalli
Dayton
Dayton Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ayman Aly El-Sheikh
Toledo
ProMedica Toledo Hospital / Russell J Ebeid Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Jamie L. Dargart
Phone: 419-824-1842

Oklahoma

Oklahoma City
University of Oklahoma Health Sciences Center
Status: CLOSED_TO_ACCRUAL
Contact: Rene Y McNall-Knapp
Phone: 405-271-8777

Oregon

Portland
Legacy Emanuel Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Janice Faye Olson
Phone: 503-413-8199
Oregon Health and Science University
Status: CLOSED_TO_ACCRUAL
Contact: Susan Joy Lindemulder
Phone: 503-494-1080

Pennsylvania

Hershey
Penn State Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Lisa MacNabb McGregor
Philadelphia
Children's Hospital of Philadelphia
Status: CLOSED_TO_ACCRUAL
Contact: Rochelle Bagatell
Phone: 520-626-9008
Saint Christopher's Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Gregory Emmett Halligan
Pittsburgh
Children's Hospital of Pittsburgh of UPMC
Status: CLOSED_TO_ACCRUAL
Contact: Jean M. Tersak

Puerto Rico

San Juan
San Jorge Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Luis A. Clavell

South Carolina

Columbia
Prisma Health Richland Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Stuart Louis Cramer
Phone: 803-434-3680
Greenville
BI-LO Charities Children's Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Nichole Leigh Bryant

South Dakota

Sioux Falls
Sanford USD Medical Center - Sioux Falls
Status: CLOSED_TO_ACCRUAL
Contact: Kayelyn Jean Wagner
Phone: 605-328-1367

Tennessee

Knoxville
East Tennessee Childrens Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Ray C. Pais
Phone: 865-541-8266
Nashville
The Children's Hospital at TriStar Centennial
Status: CLOSED_TO_ACCRUAL
Contact: Haydar A. Frangoul
Phone: 800-811-8480
Vanderbilt University / Ingram Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Devang J Pastakia
Phone: 800-811-8480

Texas

Austin
Dell Children's Medical Center of Central Texas
Status: CLOSED_TO_ACCRUAL
Contact: Amy Fowler Tellinghuisen
Dallas
Medical City Dallas Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Stanton Carl Goldman
Phone: 972-566-5588
UT Southwestern / Simmons Cancer Center-Dallas
Status: CLOSED_TO_ACCRUAL
Contact: Tanya Carens Watt
Phone: 214-648-7097
Fort Worth
Cook Children's Medical Center
Status: CLOSED_TO_ACCRUAL
Contact: Mary Meaghan Petty Granger
Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Jennifer Haunani Foster
Phone: 713-798-1354
Lubbock
Covenant Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Kishor Mallikarjun Bhende
Phone: 806-775-8590
San Antonio
Children's Hospital of San Antonio
Status: CLOSED_TO_ACCRUAL
Contact: Timothy C. Griffin
Phone: 800-248-1199
Methodist Children's Hospital of South Texas
Status: CLOSED_TO_ACCRUAL
Contact: Vinod Kumar Gidvani-Diaz

Utah

Salt Lake City
Primary Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Phillip Evan Barnette

Vermont

Burlington
University of Vermont and State Agricultural College
Status: CLOSED_TO_ACCRUAL
Contact: Alan Charles Homans
Phone: 802-656-8990

Virginia

Charlottesville
University of Virginia Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: William Carl Petersen
Phone: 434-243-6322
Norfolk
Children's Hospital of The King's Daughters
Status: CLOSED_TO_ACCRUAL
Contact: Eric Jeffrey Lowe
Richmond
Virginia Commonwealth University / Massey Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Gita Vasers Massey

Washington

Seattle
Seattle Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Douglas S. Hawkins
Spokane
Providence Sacred Heart Medical Center and Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Judy L. Felgenhauer

West Virginia

Morgantown
West Virginia University Healthcare
Status: CLOSED_TO_ACCRUAL
Contact: Stephan R. Paul
Phone: 304-293-7374

Wisconsin

Madison
University of Wisconsin Carbone Cancer Center
Status: CLOSED_TO_ACCRUAL
Contact: Kenneth Brian De Santes
Phone: 800-622-8922
Marshfield
Marshfield Medical Center-Marshfield
Status: CLOSED_TO_ACCRUAL
Contact: Michael John McManus
Phone: 800-782-8581
Milwaukee
Children's Hospital of Wisconsin
Status: CLOSED_TO_ACCRUAL
Contact: Nathan J. Schloemer
Phone: 414-955-4727

Alberta

Calgary
Alberta Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Douglas R. Strother
Edmonton
University of Alberta Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Sarah Jane McKillop
Phone: 780-407-6615

British Columbia

Vancouver
British Columbia Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: David Bryan Dix

Manitoba

Winnipeg
CancerCare Manitoba
Status: CLOSED_TO_ACCRUAL
Contact: Tanya Renae Brown
Phone: 306-766-2213

Newfoundland and Labrador

Saint John's
Janeway Child Health Centre
Status: CLOSED_TO_ACCRUAL
Contact: Lisa Anne Goodyear
Phone: 866-722-1126

Nova Scotia

Halifax
IWK Health Centre
Status: CLOSED_TO_ACCRUAL
Contact: Conrad Vincent Fernandez
Phone: 902-470-8394

Ontario

Hamilton
McMaster Children's Hospital at Hamilton Health Sciences
Status: CLOSED_TO_ACCRUAL
Contact: Carol A. Portwine
London
Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Shayna M. Zelcer
Ottawa
Children's Hospital of Eastern Ontario
Status: CLOSED_TO_ACCRUAL
Contact: Donna Lynn Johnston
Toronto
Hospital for Sick Children
Status: CLOSED_TO_ACCRUAL
Contact: Meredith S. Irwin
Phone: 416-813-7654ext2027

Quebec

Montreal
Centre Hospitalier Universitaire Sainte-Justine
Status: CLOSED_TO_ACCRUAL
Contact: Yvan Samson
Phone: 514-345-4931
The Montreal Children's Hospital of the MUHC
Status: CLOSED_TO_ACCRUAL
Contact: Sharon Barbara Abish
Quebec
Centre Hospitalier Universitaire de Quebec
Status: CLOSED_TO_ACCRUAL
Contact: Bruno Michon

Australia

Herston
Royal Children's Hospital-Brisbane
Status: CLOSED_TO_ACCRUAL
Contact: Site Public Contact
Phone: 888-823-5923
Perth
Princess Margaret Hospital for Children
Status: CLOSED_TO_ACCRUAL
Contact: Marianne Barnetson Phillips
Phone: (08) 9340 8222
Randwick
Sydney Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Geoffrey Brian McCowage
Phone: (02) 9845 8183
South Brisbane
Queensland Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Helen Irving
Westmead
The Children's Hospital at Westmead
Status: CLOSED_TO_ACCRUAL
Contact: Geoffrey Brian McCowage
Phone: (02) 9845 8183

New Zealand

Christchurch
Christchurch Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Mark Andrew Winstanley
Grafton
Starship Children's Hospital
Status: CLOSED_TO_ACCRUAL
Contact: Mark Andrew Winstanley

PRIMARY OBJECTIVES:

I. To identify whether temsirolimus or ch14.18 (dinutuximab) is the optimal therapeutic agent to consider for further testing in a future Phase III randomized trial for treatment of newly diagnosed high-risk neuroblastoma.

II. To determine the response rate of patients with relapsed, refractory or progressive neuroblastoma following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab) and to compare this with the known response rate of patients treated with irinotecan and temozolomide alone.

EXPLORATORY OBJECTIVES:

I. To compare the response rates (RR) for patients receiving temsirolimus or ch14.18 (dinutuximab) in combination with irinotecan (irinotecan hydrochloride) and temozolomide.

II. To compare the progression free survival (PFS) and overall survival (OS) rates for patients receiving temsirolimus or ch14.18 (dinutuximab) in combination with irinotecan and temozolomide.

III. To compare the toxicities associated with temsirolimus or ch14.18 (dinutuximab) when combined with irinotecan and temozolomide in patients with refractory, relapsed or progressive neuroblastoma.

IV. To compare the ability to maintain intended dose intensity of all agents when temsirolimus or ch14.18 (dinutuximab) is combined with irinotecan and temozolomide in patients with refractory, relapsed or progressive neuroblastoma.

V. To determine the concordance between tumor responses as defined by standard International Neuroblastoma Response Criteria (INRC) versus response per the revised INRC.

VI. To study the clinical relevance of naturally occurring anti-glycan antibodies in patients receiving ch14.18 (dinutuximab) antibody.

VII. To study the clinical relevance of natural killer (NK) receptor natural cytotoxicity triggering receptor 3 (NKp30) isoforms in patients receiving ch14.18 (dinutuximab) antibody or temsirolimus.

VIII. To study the association between host factors and response to irinotecan, temozolomide and ch14.18 (dinutuximab).

IX. To characterize the tumor immune-microenvironment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab).

X. To study the association between changes in the tumor immune-microenvironment (gene expression; immune effector cells, activities and signaling molecules; immune target expression) with response following treatment with irinotecan, temozolomide and ch14.18 (dinutuximab).

XI. To study the association between tumor genomic and transcriptomic aberrations as well as levels of circulating ganglioside (GD2) with response to irinotecan, temozolomide and ch14.18 (dinutuximab).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I (CLOSED TO ACCRUAL 06/17/2016): Patients receive temozolomide orally (PO) on days 1-5, irinotecan hydrochloride intravenously (IV) over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8.

ARM II: Patients receive temozolomide PO on days 1-5, irinotecan hydrochloride over 90 minutes on days 1-5, dinutuximab IV over 10-20 hours on days 2-5, and sargramostim subcutaneously (SC) or IV over 2 hours on days 6-12.

In both arms, treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Children's Oncology Group

Principal Investigator
Rajen Mody

  • Primary ID ANBL1221
  • Secondary IDs NCI-2012-03125, CDR0000745188, COG-ANBL1221, PANBL1221_A08PAMDREVW01
  • Clinicaltrials.gov ID NCT01767194