A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects

Last updated: February 15, 2023
Sponsor: Jubilant DraxImage Inc.
Overall Status: Active - Recruiting

Phase

2

Condition

Neoplasms

Neuroblastoma

Treatment

N/A

Clinical Study ID

NCT03561259
MIBG 2014-01
  • Ages > 1
  • All Genders

Study Summary

The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in combination with Vorinostat in patients with Recurrent or Progressive neuroblastoma

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on RevisedINRC criteria at the time of study enrollment with recurrent or progressive disease atany time prior to enrollment, regardless of overall response to frontline therapy,where frontline therapy includes a minimum of 4 cycles of induction therapy at anytime prior to enrollment.
  2. May have had prior 131I-MIBG therapy, provided:
  3. It has been at least 6 months from the date of last 131I-MIBG ;
  4. Response was other than progressive disease on first restaging after 131I-MIBG ;
  5. Prior 131I-MIBG was given as monotherapy and not in combination with systemicanticancer agents;
  6. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
  7. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions onan (123I)-iobenguane scan, or
  8. any progressive non-iobenguane avid lesion is proven by biopsy to be anon-neuroblastoma lesion.
  9. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown byroutine imaging and confirmed by the investigator.
  10. Adequate cryopreserved autologous peripheral blood stem cells or bone marrow (at least 2 aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment).
  11. If a male, must agree to use an adequate contraception method as deemed appropriate bythe Investigator (e.g., vasectomy, condoms) or partner using effective contraceptionand to not donate sperm during the study and for 90 days after receiving the last doseof study drug.
  12. If a female of childbearing potential, have a negative serum pregnancy test resultprior to each dosing and, if sexually active, be practicing an effective method ofbirth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or acervical cap) with intravaginal spermicidal foam, cream or gel], or male partnersterilization throughout the study.
  13. Age at study entry ≥1 year.
  14. Previous platelet transfusions are permitted, as long as the subject has a plateletcount ≥50,000/μL without transfusion support for at least 1 week.
  15. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
  16. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
  17. Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age,and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartateaminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit ofnormal (for all sites, the upper limit of normal for alanine aminotransferase isdefined as 45 U/L).
  18. Normal thyroid function as measured by T4 or TSH or have abnormal results that are notconsidered clinically important by the Investigator or may be receiving levothyroxine.
  19. Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior toVisit 1 (Baseline).
  20. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky PerformanceStatus Performance Status (for subjects 1 to 16 years of age) ≥50%.
  21. Full recovery from the toxic effects of any prior therapy.
  22. Coagulation Function:
  23. International Normalized Ratio (INR) < 1.5
  24. Partial thromboplastin time (PTT) < 1.5 times upper limit of normal.

Exclusion

Exclusion Criteria:

  1. Subjects within 5 half-lives after any antibody-based immunotherapy, or have notrecovered from effects of any biologic therapy.
  2. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
  3. Subjects who have had an allogeneic stem cell treatment less than 4 months from Visit 1 are excluded. Those who have received allogeneic stem cell treatment more than 4months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible.
  4. Subjects must not have received radiation for a minimum of 2 weeks prior to studyenrollment. Subjects whose only site(s) of disease have been radiated are eligible aslong as the subject has MIBG avidity 2 weeks after completion of radiation. A minimumof 12 weeks prior to study enrollment is required following prior large fieldradiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space)
  5. History of total body irradiation.
  6. Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 eitherby creatinine clearance or radioisotope direct measurement or by calculation with theSchwartz formula
  7. Subjects who are on hemodialysis.
  8. Pregnancy or breastfeeding.
  9. Significant active infections including active hepatitis B, or hepatitis C infection,or known infection with human immunodeficiency virus (HIV) (testing for HIV is notrequired prior to study entry).
  10. Clinically important cardiac, pulmonary, and hepatic impairment.
  11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteriaand otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
  12. Since valproic acid has HDAC inhibitory activity, patients must not have receivedvalproic acid within 30 days of study entry.
  13. Since vorinostat may prolong the QT interval, patients must not be receivingother medications known to prolong the QT interval at the time of study entry .Pentamidine must not have been received within 1 week of study enrollment.
  14. Patients with a history of deep venous thrombosis that was not associated withthe presence of a central venous catheter.
  15. Patients who are receiving Coumadin.

Study Design

Total Participants: 60
Study Start date:
October 21, 2019
Estimated Completion Date:
April 30, 2025

Study Description

OPTIMUM (MIBG 2014-01) is a Phase II, Two arm, non-randomized, open-label study of therapeutic 131I-iobenguane (131I-MIBG) as single agent or in combination with Vorinostat for the treatment of neuroblastoma. The study will be conducted in male and female subjects, greater than 1 year of age, with iobenguane avid, who have recurrent or progressive disease, regardless of overall response to frontline therapy, where frontline therapy includes a minimum of 4 cycles of induction therapy at any time prior to enrollment, high-risk neuroblastoma.

Subjects who are eligible for combination treatment will receive vorinostat 180 mg/m2/dose (maximum dose 400 mg) once daily for 14 days (Day -1 to Day 12) continuously.

Subjects will receive 18 mCi/kg of 131I-MIBG intravenously on Day 1.

If the subject qualifies, the subject will receive the second treatment course of 131I-MIBG in combination with vorinostat or 131I-MIBG alone (no sooner than 6 weeks following first treatment course). Subject must have an overall response of stable disease or better, as assessed by the Investigator, and meet certain predefined criteria to receive the second course of treatment.

Following a screening period of up to 4 weeks, the duration in the study treatment phase for an individual subject, who receives two treatments, is up to 26 weeks. For an individual subject, who receives one treatment only, the duration of the treatment phase is 16 weeks. In addition, there is a 2-year follow-up after the treatment phase, during which assessments will be performed to assess disease progression, as well as record adverse events.

Connect with a study center

  • Stanford University

    Palo Alto, California 94304
    United States

    Site Not Available

  • UCSF Pediatric Hematology/Oncology

    San Francisco, California 94158
    United States

    Active - Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado 80045
    United States

    Active - Recruiting

  • Nemours Children's Specialty Care

    Jacksonville, Florida 32207
    United States

    Active - Recruiting

  • University of Chicago Medical Center

    Chicago, Illinois 60637
    United States

    Active - Recruiting

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa 52242
    United States

    Active - Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts 02215
    United States

    Active - Recruiting

  • University of Minnesota

    Minneapolis, Minnesota 55455
    United States

    Active - Recruiting

  • Washington University Medical Center in St. Louis

    Saint Louis, Missouri 63110
    United States

    Active - Recruiting

  • Northwell Health /Cohen Children's Medical Center

    New Hyde Park, New York 11040
    United States

    Active - Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York 10065
    United States

    Active - Recruiting

  • Carolinas Medical Center/Levine Children's Hospital (Atrium Health)

    Charlotte, North Carolina 28203
    United States

    Active - Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio 45229
    United States

    Active - Recruiting

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania 15224
    United States

    Active - Recruiting

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania 15224
    United States

    Active - Recruiting

  • University of Texas Southwestern Medical Center, Children's Health

    Dallas, Texas 75235
    United States

    Active - Recruiting

  • Cook Children's Hematology/Oncology Center

    Fort Worth, Texas 76104
    United States

    Active - Recruiting

  • Texas Children's Hospital

    Houston, Texas 77030
    United States

    Active - Recruiting

  • Seattle Children's Hospital

    Seattle, Washington 98105
    United States

    Active - Recruiting

  • University of Wisconsin, American Family Children's Hospital and Clinical Science Center

    Madison, Wisconsin 53792
    United States

    Active - Recruiting

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