NCT02035137

Brief Summary

This study will compare three treatment regimens containing metaiodobenzylguanidine (MIBG) and compare their effects on tumor response and associated side effects, to determine if one therapy is better than the other for people diagnosed with relapsed or persistent neuroblastoma.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
114

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Jul 2014

Longer than P75 for phase_2

Geographic Reach
2 countries

14 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 7, 2014

Completed
7 days until next milestone

First Posted

Study publicly available on registry

January 14, 2014

Completed
6 months until next milestone

Study Start

First participant enrolled

July 1, 2014

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 26, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 26, 2021

Completed
1.3 years until next milestone

Results Posted

Study results publicly available

June 8, 2022

Completed
Last Updated

June 8, 2022

Status Verified

May 1, 2022

Enrollment Period

6.7 years

First QC Date

January 7, 2014

Results QC Date

February 24, 2022

Last Update Submit

May 16, 2022

Conditions

Outcome Measures

Primary Outcomes (1)

  • Objective Tumor Response After One Course of Therapy

    To identify the MIBG treatment regimen associated with the highest overall response rate after one course of treatment on the three arms. The response evaluation was based on central review (intent to treat analysis). Responders defined as meeting CR/MRD/PR criteria. Response was based on NANT response criteria v1.2 (https://doi.org/10.1002/pbc.26940). RECST 1.1 criteria was used for measurable tumors with PR criteria \> 30% decrease in target tumor size. Curie score was used with PR criteria \> 50% decrease in Curie score. Complete Response- disappearance of all target lesions, Curie score of 0 and no detectable bone marrow disease. Overall Response (OR)=CR+PR.

    43-50 days from study day 1

Secondary Outcomes (1)

  • Number of Participants With Grade 3 or Greater Non-hematologic Toxicities

    All toxicities from enrollment through 30 days following end of protocol therapy, an average of 6 months

Study Arms (3)

Single-Agent 131I-MIBG

ACTIVE COMPARATOR

Single-agent 131I-MIBG (Arm A) 18 mCi/kg 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15.

Radiation: 131I-MIBG

131I-MIBG with Vincristine/Irinotecan

ACTIVE COMPARATOR

Vincristine / irinotecan / 131I-MIBG (Arm B): vincristine 2 mg/m2 (maximum dose 2 mg) intravenously on Day 0; irinotecan 50 mg/m2 (maximum dose 100 mg) intravenously on Days 0 to 4. Patients will also receive diarrhea prophylaxis with cefixime 8 mg/kg/day orally on Days -1 to +6. 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.

Radiation: 131I-MIBGDrug: VincristineDrug: Irinotecan

131I-MIBG with Vorinostat

ACTIVE COMPARATOR

Vorinostat / 131I-MIBG (Arm C); vorinostat 180 mg/m2 (maximum dose 400 mg) orally once daily on Days -1 to +12 (14 total doses). 131I-MIBG, 18 mCi/kg on Day 1 and autologous stem cell infusion on Day 15.

Radiation: 131I-MIBGDrug: Vorinostat

Interventions

131I-MIBGRADIATION
Also known as: 131I-Metaiodobenzylguanidine, Iobenguane sulfate, m-Iodobenzylguanidine sulfate, MIBG
131I-MIBG with Vincristine/Irinotecan131I-MIBG with VorinostatSingle-Agent 131I-MIBG
131I-MIBG with Vincristine/Irinotecan
131I-MIBG with Vincristine/Irinotecan
Also known as: Zolinza
131I-MIBG with Vorinostat

Eligibility Criteria

Age2 Years - 30 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patients must be \> 24 months and \< 30 years of age when registered on study.
  • Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to frontline therapy frontline therapy with \> 3 residual lesions on end-induction MIBG scan.
  • Patients must have evidence of MIBG uptake into tumor at ≥ one site within 4 weeks prior to entry on study and subsequent to any intervening therapy.
  • Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
  • Patients must have a dose of unpurged peripheral blood stem cells is 2.0 x 106 viable CD34+ cells/kg available.

You may not qualify if:

  • They have had previous I-131 MIBG therapy
  • They have other medical problems that could get much worse with this treatment.
  • They are pregnant or breast feeding.
  • They have a history of a venous or arterial thrombosis that was not associated to a central line.
  • They have active infections such as hepatitis or fungal infections.
  • They have active diarrhea.
  • They have had an allogeneic stem cell transplant (received stem cell from someone else)
  • They can't cooperate with the special precautions that are needed for this trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (14)

Childrens Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

Lucile Salter Packer Children's Hospital

Palo Alto, California, 94304, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

Children Hospital of Colorado

Aurora, Colorado, 80045, 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

Ann Arbor, Michigan, 48109, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, 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 Healthcare System

Fort Worth, Texas, 76104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

Related Publications (1)

  • DuBois SG, Granger MM, Groshen S, Tsao-Wei D, Ji L, Shamirian A, Czarnecki S, Goodarzian F, Berkovich R, Shimada H, Villablanca JG, Vo KT, Pinto N, Mosse YP, Maris JM, Shusterman S, Cohn SL, Goldsmith KC, Weiss B, Yanik GA, Twist CJ, Irwin MS, Haas-Kogan DA, Park JR, Marachelian A, Matthay KK. Randomized Phase II Trial of MIBG Versus MIBG, Vincristine, and Irinotecan Versus MIBG and Vorinostat for Patients With Relapsed or Refractory Neuroblastoma: A Report From NANT Consortium. J Clin Oncol. 2021 Nov 1;39(31):3506-3514. doi: 10.1200/JCO.21.00703. Epub 2021 Jul 16.

MeSH Terms

Conditions

Neuroblastoma

Interventions

3-IodobenzylguanidineVincristineIrinotecanVorinostat

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, PeripheralNeuroectodermal Tumors, PrimitiveNeoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

GuanidinesAmidinesOrganic ChemicalsIodobenzenesBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsHydrocarbons, IodinatedHydrocarbons, HalogenatedVinca AlkaloidsSecologanin Tryptamine AlkaloidsIndole AlkaloidsAlkaloidsHeterocyclic CompoundsIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingIndolizidinesIndolizinesCamptothecinAnilidesAmidesAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic Acids

Results Point of Contact

Title
NANT Medical Director
Organization
New Advances in Neuroblastoma Therapy

Study Officials

  • Steven DuBois, MD

    Dana-Farber Cancer Institute

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 7, 2014

First Posted

January 14, 2014

Study Start

July 1, 2014

Primary Completion

February 26, 2021

Study Completion

February 26, 2021

Last Updated

June 8, 2022

Results First Posted

June 8, 2022

Record last verified: 2022-05

Locations