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

• ClinicalTrials.gov Identifier: NCT01767194
• Recruitment Status: Completed
• First Posted: January 14, 2013
• Results First Posted: November 18, 2019
• Last Update Posted: October 24, 2022
• Sponsor: National Cancer Institute (NCI)
• Collaborator: United Therapeutics
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Ganglioneuroblastoma; Recurrent Neuroblastoma	Biological: Dinutuximab; Drug: Irinotecan Hydrochloride; Other: Laboratory Biomarker Analysis; Biological: Sargramostim; Drug: Temozolomide; Drug: Temsirolimus	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 73 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Randomized Trial of Irinotecan/Temozolomide With Temsirolimus (NSC# 683864) or Chimeric 14.18 Antibody (Ch14.18) (NSC# 764038) in Children With Refractory, Relapsed or Progressive Neuroblastoma
• Actual Study Start Date: February 12, 2013
• Actual Primary Completion Date: June 30, 2018
• Actual Study Completion Date: September 30, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm I (temozolomide, irinotecan hydrochloride, temsirolimus); CLOSED TO ACCRUAL 06/17/2016 Patients receive temozolomide PO on days 1-5, irinotecan hydrochloride IV over 90 minutes on days 1-5, and temsirolimus IV over 30 minutes on days 1 and 8.	Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto; Camptosar; Camptothecin 11; Camptothecin-11; CPT 11; CPT-11; Irinomedac; Irinotecan Hydrochloride Trihydrate; Irinotecan Monohydrochloride Trihydrate; U-101440E; Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Temozolomide; Given PO; Other Names: CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Methazolastone; RP-46161; SCH 52365; Temcad; Temodal; Temodar; Temomedac; TMZ; Drug: Temsirolimus; Given IV; Other Names: CCI-779; CCI-779 Rapamycin Analog; Cell Cycle Inhibitor 779; Rapamycin Analog; Rapamycin Analog CCI-779; Torisel
Experimental: Arm II (temozolomide, irinotecan hydrochloride, dinutuximab); 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 SC or IV over 2 hours on days 6-12.	Biological: Dinutuximab; Given IV; Other Names: Ch 14.18UTC; Ch14.18; MOAB Ch14.18; monoclonal antibody Ch14.18; Unituxin; Drug: Irinotecan Hydrochloride; Given IV; Other Names: Campto; Camptosar; Camptothecin 11; Camptothecin-11; CPT 11; CPT-11; Irinomedac; Irinotecan Hydrochloride Trihydrate; Irinotecan Monohydrochloride Trihydrate; U-101440E; Other: Laboratory Biomarker Analysis; Optional correlative studies; Biological: Sargramostim; Given SC or IV; Other Names: 23-L-Leucinecolony-Stimulating Factor 2; DRG-0012; Leukine; Prokine; rhu GM-CFS; Sagramostim; Sargramostatin; Drug: Temozolomide; Given PO; Other Names: CCRG-81045; Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-; M & B 39831; M and B 39831; Methazolastone; RP-46161; SCH 52365; Temcad; Temodal; Temodar; Temomedac; TMZ

Outcome Measures

Primary Outcome Measures :

1. Percentage of Randomized Patients Who Are Responders [ Time Frame: Up to the first 6 cycles of treatment ]
   The percentage of patients who are responders will be tabulated, including a 95% confidence interval on the response rate. Responders are defined as patients who achieve a best overall response of complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Neuroblastoma Response Criteria (INRC). Per INRC: CR= Disappearance of all target lesions. No evidence of tumor at any site; VGPR= >90% decrease of the disease measurement for CT/MRI target lesions. All pre-existing bone lesions with CR by MIBG; MIBG scan can be stable disease (SD) or CR in soft tissue lesions corresponding to lesions on CT/MRI. CR in bone marrow. No new sites of tumor; PR= >=30% decrease in the disease measurement for CT/MRI target lesions. Bone marrow with CR. MIBG with either PR/CR in bone lesions; MIBG may be SD or CR in soft tissue lesions corresponding to lesions on CT/MRI. Homovanillic acid (HVA)/Vanillylmandelic acid (VMA) may still be elevated.
2. Percentage of Patients in the Dinutuximab Arm Who Are Responders [ Time Frame: Up to the first 6 cycles of treatment ]
   Percentage of patients who are responders to therapy with dinutuximab will be tabulated, including a 95% confidence interval on the response rate. Responders are defined as patients who achieve a best overall response of complete response (CR), very good partial response (VGPR), or partial response (PR) per the International Neuroblastoma Response Criteria (INRC). Per INRC: CR= Disappearance of all target lesions. No evidence of tumor at any site; VGPR= >90% decrease of disease measurement for CT/MRI target lesions. All pre-existing bone lesions with CR by MIBG; MIBG scan can be stable disease (SD) or CR in soft tissue lesions corresponding to lesions on CT/MRI. CR in bone marrow. No new sites of tumor; PR= ≥30% decrease in disease measurement for CT/MRI target lesions. Bone marrow with CR. MIBG with either PR/CR in bone lesions; MIBG may be SD or CR in soft tissue lesions corresponding to lesions on CT/MRI. Homovanillic acid (HVA)/ Vanillylmandelic acid (VMA) may still be elevated.

Other Outcome Measures:

1. Progression-free Survival [ Time Frame: Up to 3 years ]
   Kaplan-Meier method will be used to estimate progression-free survival. Progression-free survival will be defined as the time from enrollment to relapse, progressive disease, or death attributable to tumor or treatment.
2. Overall Survival [ Time Frame: Up to 3 years ]
   Kaplan-Meier method will be used to estimate overall survival. Overall survival is defined as the time from enrollment on the study until death.
3. Occurrence of Unacceptable Toxicities [ Time Frame: Up to 1 year ]
   The proportion of patients with at least one grade 3 or higher toxicity, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
4. Ability to Maintain Intended Treatment Without a Dose Reduction or Going Off Protocol Therapy for Toxicity [ Time Frame: Up to 1 year ]
   The proportion of patients who required a dose modification or went off protocol therapy for toxicity will be calculated for each treatment group.
5. Overall Response [ Time Frame: Up to the first 6 cycles of treatment ]
   The proportion of patients achieving each type of overall response (complete response, partial response, stable disease, progressive disease) will be calculated according to the International Neuroblastoma Response Criteria (INRC).

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Phoenix Childrens Hospital

Phoenix, Arizona, United States, 85016

United States, Arkansas

Arkansas Children's Hospital

Little Rock, Arkansas, United States, 72202-3591

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

United States, California

Kaiser Permanente Downey Medical Center

Downey, California, United States, 90242

Loma Linda University Medical Center

Loma Linda, California, United States, 92354

Children's Hospital Los Angeles

Los Angeles, California, United States, 90027

Valley Children's Hospital

Madera, California, United States, 93636

Kaiser Permanente-Oakland

Oakland, California, United States, 94611

Children's Hospital of Orange County

Orange, California, United States, 92868

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States, 94304

Sutter Medical Center Sacramento

Sacramento, California, United States, 95816

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States, 95817

Rady Children's Hospital - San Diego

San Diego, California, United States, 92123

UCSF Medical Center-Parnassus

San Francisco, California, United States, 94143

UCSF Medical Center-Mission Bay

San Francisco, California, United States, 94158

United States, Colorado

Children's Hospital Colorado

Aurora, Colorado, United States, 80045

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States, 80218

United States, Connecticut

Connecticut Children's Medical Center

Hartford, Connecticut, United States, 06106

Yale University

New Haven, Connecticut, United States, 06520

United States, Delaware

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States, 19803

United States, District of Columbia

MedStar Georgetown University Hospital

Washington, District of Columbia, United States, 20007

Children's National Medical Center

Washington, District of Columbia, United States, 20010

United States, Florida

Lee Memorial Health System

Fort Myers, Florida, United States, 33901

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States, 33908

University of Florida Health Science Center - Gainesville

Gainesville, Florida, United States, 32610

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States, 33021

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States, 32207

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States, 33136

Nicklaus Children's Hospital

Miami, Florida, United States, 33155

AdventHealth Orlando

Orlando, Florida, United States, 32803

Nemours Children's Clinic - Orlando

Orlando, Florida, United States, 32806

Nemours Children's Hospital

Orlando, Florida, United States, 32827

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States, 32504

Johns Hopkins All Children's Hospital

Saint Petersburg, Florida, United States, 33701

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States, 33607

Saint Mary's Hospital

West Palm Beach, Florida, United States, 33407

United States, Georgia

Children's Healthcare of Atlanta - Egleston

Atlanta, Georgia, United States, 30322

Memorial Health University Medical Center

Savannah, Georgia, United States, 31404

United States, Hawaii

University of Hawaii Cancer Center

Honolulu, Hawaii, United States, 96813

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States, 96826

United States, Idaho

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States, 83712

United States, Illinois

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States, 60611

University of Illinois

Chicago, Illinois, United States, 60612

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States, 60637

Loyola University Medical Center

Maywood, Illinois, United States, 60153

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States, 60453

Saint Jude Midwest Affiliate

Peoria, Illinois, United States, 61637

Southern Illinois University School of Medicine

Springfield, Illinois, United States, 62702

United States, Indiana

Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, United States, 46260

United States, Iowa

Blank Children's Hospital

Des Moines, Iowa, United States, 50309

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States, 52242

United States, Kentucky

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States, 40536

Norton Children's Hospital

Louisville, Kentucky, United States, 40202

United States, Louisiana

Children's Hospital New Orleans

New Orleans, Louisiana, United States, 70118

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States, 70121

United States, Maine

Eastern Maine Medical Center

Bangor, Maine, United States, 04401

United States, Maryland

Sinai Hospital of Baltimore

Baltimore, Maryland, United States, 21215

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

C S Mott Children's Hospital

Ann Arbor, Michigan, United States, 48109

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States, 48201

Ascension Saint John Hospital

Detroit, Michigan, United States, 48236

Michigan State University Clinical Center

East Lansing, Michigan, United States, 48824-7016

Helen DeVos Children's Hospital at Spectrum Health

Grand Rapids, Michigan, United States, 49503

United States, Minnesota

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States, 55404

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States, 55455

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

United States, Mississippi

University of Mississippi Medical Center

Jackson, Mississippi, United States, 39216

United States, Missouri

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States, 64108

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Mercy Hospital Saint Louis

Saint Louis, Missouri, United States, 63141

United States, Nebraska

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States, 68114

University of Nebraska Medical Center

Omaha, Nebraska, United States, 68198

United States, Nevada

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States, 89102

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States, 89109

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States, 89135

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States, 89144

Nevada Cancer Research Foundation NCORP

Las Vegas, Nevada, United States, 89169

United States, New Hampshire

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States, 03756

United States, New Jersey

Hackensack University Medical Center

Hackensack, New Jersey, United States, 07601

Morristown Medical Center

Morristown, New Jersey, United States, 07960

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States, 08903

United States, New Mexico

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States, 87102

United States, New York

Albany Medical Center

Albany, New York, United States, 12208

Montefiore Medical Center - Moses Campus

Bronx, New York, United States, 10467

Roswell Park Cancer Institute

Buffalo, New York, United States, 14263

NYU Winthrop Hospital

Mineola, New York, United States, 11501

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States, 11040

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, United States, 10032

University of Rochester

Rochester, New York, United States, 14642

State University of New York Upstate Medical University

Syracuse, New York, United States, 13210

New York Medical College

Valhalla, New York, United States, 10595

United States, North Carolina

Mission Hospital

Asheville, North Carolina, United States, 28801

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States, 27599

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States, 28203

Duke University Medical Center

Durham, North Carolina, United States, 27710

United States, North Dakota

Sanford Broadway Medical Center

Fargo, North Dakota, United States, 58122

United States, Ohio

Children's Hospital Medical Center of Akron

Akron, Ohio, United States, 44308

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States, 44106

Nationwide Children's Hospital

Columbus, Ohio, United States, 43205

Dayton Children's Hospital

Dayton, Ohio, United States, 45404

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, United States, 43606

United States, Oklahoma

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Legacy Emanuel Children's Hospital

Portland, Oregon, United States, 97227

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Penn State Children's Hospital

Hershey, Pennsylvania, United States, 17033

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States, 19104

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States, 19134

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States, 15224

United States, South Carolina

Prisma Health Richland Hospital

Columbia, South Carolina, United States, 29203

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States, 29605

United States, South Dakota

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States, 57117-5134

United States, Tennessee

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States, 37916

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States, 37203

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States, 37232

United States, Texas

Dell Children's Medical Center of Central Texas

Austin, Texas, United States, 78723

Medical City Dallas Hospital

Dallas, Texas, United States, 75230

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States, 75390

Cook Children's Medical Center

Fort Worth, Texas, United States, 76104

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States, 77030

Covenant Children's Hospital

Lubbock, Texas, United States, 79410

Children's Hospital of San Antonio

San Antonio, Texas, United States, 78207

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States, 78229

United States, Utah

Primary Children's Hospital

Salt Lake City, Utah, United States, 84113

United States, Vermont

University of Vermont and State Agricultural College

Burlington, Vermont, United States, 05405

United States, Virginia

University of Virginia Cancer Center

Charlottesville, Virginia, United States, 22908

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States, 23507

Virginia Commonwealth University/Massey Cancer Center

Richmond, Virginia, United States, 23298

United States, Washington

Seattle Children's Hospital

Seattle, Washington, United States, 98105

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States, 99204

United States, West Virginia

West Virginia University Healthcare

Morgantown, West Virginia, United States, 26506

United States, Wisconsin

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States, 53792

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States, 54449

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Australia, New South Wales

Sydney Children's Hospital

Randwick, New South Wales, Australia, 2031

The Children's Hospital at Westmead

Westmead, New South Wales, Australia, 2145

Australia, Queensland

Royal Children's Hospital-Brisbane

Herston, Queensland, Australia, 4029

Queensland Children's Hospital

South Brisbane, Queensland, Australia, 4101

Australia, Western Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia, 6008

Canada, Alberta

Alberta Children's Hospital

Calgary, Alberta, Canada, T3B 6A8

University of Alberta Hospital

Edmonton, Alberta, Canada, T6G 2B7

Canada, British Columbia

British Columbia Children's Hospital

Vancouver, British Columbia, Canada, V6H 3V4

Canada, Manitoba

CancerCare Manitoba

Winnipeg, Manitoba, Canada, R3E 0V9

Canada, Newfoundland and Labrador

Janeway Child Health Centre

Saint John's, Newfoundland and Labrador, Canada, A1B 3V6

Canada, Nova Scotia

IWK Health Centre

Halifax, Nova Scotia, Canada, B3K 6R8

Canada, Ontario

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada, L8N 3Z5

Children's Hospital

London, Ontario, Canada, N6A 5W9

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada, K1H 8L1

Hospital for Sick Children

Toronto, Ontario, Canada, M5G 1X8

Canada, Quebec

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada, H3H 1P3

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada, H3T 1C5

Canada

Centre Hospitalier Universitaire de Quebec

Quebec, Canada, G1V 4G2

New Zealand

Starship Children's Hospital

Grafton, Auckland, New Zealand, 1145

Christchurch Hospital

Christchurch, New Zealand, 8011

Puerto Rico

San Jorge Children's Hospital

San Juan, Puerto Rico, 00912

Sponsors and Collaborators

National Cancer Institute (NCI)

United Therapeutics

Investigators

• Principal Investigator: Rajen Mody; Children's Oncology Group

  Study Documents (Full-Text)

Documents provided by National Cancer Institute (NCI):

Study Protocol and Statistical Analysis Plan  [PDF] May 19, 2017

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mody R, Yu AL, Naranjo A, Zhang FF, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Hank JA, Felder M, Birstler J, Sondel PM, Asgharzadeh S, Glade-Bender J, Katzenstein H, Maris JM, Park JR, Bagatell R. Irinotecan, Temozolomide, and Dinutuximab With GM-CSF in Children With Refractory or Relapsed Neuroblastoma: A Report From the Children's Oncology Group. J Clin Oncol. 2020 Jul 1;38(19):2160-2169. doi: 10.1200/JCO.20.00203. Epub 2020 Apr 28.

Mody R, Naranjo A, Van Ryn C, Yu AL, London WB, Shulkin BL, Parisi MT, Servaes SE, Diccianni MB, Sondel PM, Bender JG, Maris JM, Park JR, Bagatell R. Irinotecan-temozolomide with temsirolimus or dinutuximab in children with refractory or relapsed neuroblastoma (COG ANBL1221): an open-label, randomised, phase 2 trial. Lancet Oncol. 2017 Jul;18(7):946-957. doi: 10.1016/S1470-2045(17)30355-8. Epub 2017 May 23.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT01767194
• Other Study ID Numbers: NCI-2012-03125; NCI-2012-03125 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); CDR0000745188; ANBL1221; COG-ANBL1221; PANBL1221_A08PAMDREVW01; ANBL1221 ( Other Identifier: Children's Oncology Group ); ANBL1221 ( Other Identifier: CTEP ); U10CA180886 ( U.S. NIH Grant/Contract ); U10CA098543 ( U.S. NIH Grant/Contract )
• First Posted: January 14, 2013
• Results First Posted: November 18, 2019
• Last Update Posted: October 24, 2022
• Last Verified: October 2022

Additional relevant MeSH terms:

Neuroblastoma; Ganglioneuroblastoma; 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; Sirolimus; Irinotecan; Camptothecin; Temozolomide; Temsirolimus; Dinutuximab; MTOR Inhibitors; Sargramostim; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antifungal Agents