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A Study of Therapeutic Iobenguane (131-I) for Relapsed, High-Risk Neuroblastoma Subjects (OPTIMUM)

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ClinicalTrials.gov Identifier: NCT03561259
Recruitment Status : Recruiting
First Posted : June 19, 2018
Last Update Posted : March 1, 2019
Sponsor:
Information provided by (Responsible Party):
Jubilant DraxImage Inc.

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of 131I-MIBG in patients with neuroblastoma, who relapsed.

Condition or disease Intervention/treatment Phase
Neuroblastoma Neuroectodermal Tumors Neoplasms Drug: 131I-MIBG Phase 2

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

OPTIMUM (MIBG 2014-01) is a Phase II, single-arm, non-randomized, open-label study of therapeutic 131I-iobenguane (131I-MIBG) for the treatment of neuroblastoma. The study will be conducted in male and female subjects, greater than 1 year of age, with iobenguane avid, relapsed, high-risk neuroblastoma.

Subjects will receive 18 mCi/kg of 131I-MIBG intravenously, and if the subject qualifies, the subject will receive the second 18 mCi/kg 131I-MIBG treatment (no sooner than 6 weeks following the first therapeutic 131I-MIBG treatment). 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 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 22 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 65 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm, non-randomized, open-label study.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Single-arm Study of Therapeutic Iobenguane (131-I) for Relapsed, High-risk Neuroblastoma Subjects
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Neuroblastoma

Arm Intervention/treatment
Experimental: 131I-MIBG
131I-MIBG
Drug: 131I-MIBG
Subjects will receive 18 mCi/kg of 131I-MIBG administered via either a central or a peripheral intravenous catheter over 1.5 to 2 hours on Day 0. The maximum absolute dose of 131I-MIBG on this protocol is determined by institution therapeutic limits and will not exceed 1,000 mCi. Subjects with an overall response of stable disease or better as assessed by the Investigator, and who meet certain predefined criteria, may receive a second 18 mCi/kg 131I-MIBG treatment no sooner than 6 weeks following the first therapeutic 131I-MIBG treatment.
Other Names:
  • I-131 meta-iodobenzylguanidine
  • Iobenguane I-131 MIBG Injection




Primary Outcome Measures :
  1. Overall Response [ Time Frame: 6 weeks after the last 131I-MIBG treatment and a confirmatory assessment at least 6 weeks thereafter (at least 12 weeks from the end of treatment) ]
    Overall response (Yes/No) is based on the International Neuroblastoma Response Crtieria (INRC, published 2017). The INRC will be calculated based on 123I-iobenguane scans, CT/MRI, and bone marrow biopsies and aspirates. A "Yes" is defined as complete response, partial response or minor response. A "No" response is defined as stable disease or progressive disease.


Secondary Outcome Measures :
  1. Overall Response at 6 weeks after 131I-MIBG treatment [ Time Frame: 6 weeks after the last 131I-MIBG treatment (first or second treatment). ]
  2. Durability of Effect of Overall Response (Yes/No) [ Time Frame: For all tumour assessment data collected throughout the study (up to the end of the 2-year follow-up). ]
  3. Relative Curie Extension Score [ Time Frame: 6 weeks after the last 131I-MIBG treatment. ]
  4. Durability of Effect of Relative Curie Extension Score [ Time Frame: For all tumour assessment data collected throughout the study (up to the end of the 2-year follow-up). ]

Other Outcome Measures:
  1. Incidence of Adverse Events (CTCAE Version 5.0) [ Time Frame: Up to 22 weeks ]
  2. Incidence of Serious Adverse Events [ Time Frame: Through study completion, up to 2.5 years. ]
  3. Whole Body Radiation Dose [ Time Frame: After each 131I-MIBG treatment for up to 120 hours. ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subjects with a diagnosis of iobenguane avid, relapsed, high-risk neuroblastoma based on revised INRC criteria who have completed at least one cycle of induction and consolidation therapy with an INRC criterion of partial response or better, and then showed new progressive disease (revised INRC criteria progressive disease) as described in Park, et al. (2017).This may include one or more of the following drugs: cyclophosphamide or ifosfamide, cisplatin or carboplatin, vincristine, doxorubicin (adriamycin), etoposide, topotecan, and/or busulfan and melphalan (sometimes used during stem cell transplant) and/or immunotherapy. (If a subject is symptomatic and for logistical reasons cannot be treated immediately with 131I-MIBG, 1 to 2 cycles of "bridging chemotherapy" or immunotherapy will be permitted. If "bridging chemotherapy" or immunotherapy is applied, approximately 4 weeks will be required for reassessment of the baseline including tumor assessment.
  2. Must be therapeutic 131I-MIBG naive.
  3. All soft tissue lesions identified on CT/MRI scans must be iobenguane-avid lesions on an iobenguane (123I) scan or any non iobenguane avid lesions biopsy proven to be non-tumor lesions.
  4. 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).
  5. If a man, must agree to use an adequate contraception method as deemed appropriate by the Investigator (e.g., vasectomy, condoms) or partner using effective contraception and to not donate sperm during the study and for 90 days after receiving the last dose of study drug.
  6. If a woman of childbearing potential, have a negative serum pregnancy test result prior to each dosing and, if sexually active, be practicing an effective method of birth control [e.g., intrauterine device, double-barrier method (i.e., diaphragm, or a cervical cap) with intravaginal spermicidal foam, cream or gel], or male partner sterilization throughout the study.
  7. Age at study entry ≥1 year.
  8. Previous platelet transfusions are permitted, as long as the subject has a platelet count ≥50,000/μL without transfusion support for at least 1 week.
  9. Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
  10. An absolute neutrophil count ≥750/μL without growth factor for 5 days.
  11. Liver function parameter results: total bilirubin ≤1.5 × upper limit of normal for age, and serum glutamic-pyruvic transaminase (alanine aminotransferase) [SGPT (ALT)] and serum glutamic-oxaloacetic transaminase (aspartate aminotransferase) [SGOT (AST)] <3 × upper limit of normal (note that for ALT, the upper limit of normal for all sites is defined as 45 U/L).
  12. Normal thyroid function as measured by T4 and TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine.
  13. Cardiac Function: Ejection fraction (≥55%) documented by echocardiogram within 1 month prior to Visit 1 (baseline).
  14. Karnofsky Performance Status (for subjects >16 years of age) or the Lansky Performance Status Performance Status (for subjects 1 to 16 years of age) ≥50%.
  15. Full recovery from the toxic effects of any prior therapy.

Exclusion Criteria:

  1. Evidence of non-avid iobenguane lesions on iobenguane (123I) scan including soft tissue disease on CT/MRI that is not iobenguane-avid.
  2. Subjects with primary refractory disease.
  3. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy.
  4. Subjects that are refractory to the prior treatment regimen.
  5. Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
  6. 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 4 months from Visit 1 must have recovered and have no active graft versus host disease (GVHD) to be eligible.
  7. History of local radiation therapy within the last 3 months.
  8. History of total body irradiation.
  9. Subjects do not have adequate renal function defined as adjusted serum creatinine ≥1.5 × upper limit of normal for sex and age.
  10. Subjects who are on hemodialysis.
  11. Pregnancy or breastfeeding.
  12. Significant active infections including active hepatitis B, or hepatitis C infection, or known infection with human immunodeficiency virus (HIV) (testing for HIV is not required prior to study entry).
  13. Clinically important cardiac, pulmonary, and hepatic impairment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03561259


Contacts
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Contact: Norman LaFrance, MD,FACP 267-475-2192 MIBGclinicaltrials@jdi.jubl.com
Contact: Margaret E Hurley, MD,FRAPS (908) 273-8490 MIBG-OPTIMUM-Trial@hurleyconsulting.com

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Astrid Eder    720-777-8531    astrid.eder@coloradochildrens.org   
Principal Investigator: Margaret Macy, MD         
United States, Texas
University of Texas Southwestern Medical Center, Children's Health Recruiting
Dallas, Texas, United States, 75235
Contact: Beverly Kleiber, PhD, CCRP    214-456-1003    beverly.kleiber@childrens.com   
Principal Investigator: Tanya Watt, MD         
United States, Washington
Seattle Children's Hospital Recruiting
Seattle, Washington, United States, 98105
Contact: Laura Hill    206-884-3002    laura.hill@seattlechildrens.org   
Principal Investigator: Navin Pinto, MD         
Sponsors and Collaborators
Jubilant DraxImage Inc.
Investigators
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Study Director: Norman LaFrance, MD,FACP Jubilant DraxImage Inc.
Study Director: Alexandre Brkovic, PhD Jubilant DraxImage Inc.

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Responsible Party: Jubilant DraxImage Inc.
ClinicalTrials.gov Identifier: NCT03561259     History of Changes
Other Study ID Numbers: MIBG 2014-01
First Posted: June 19, 2018    Key Record Dates
Last Update Posted: March 1, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jubilant DraxImage Inc.:
Iobenguane Avid High-risk Neuroblastoma
3-Iodobenzylguanidine
Radiopharmaceutical

Additional relevant MeSH terms:
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Neuroblastoma
3-Iodobenzylguanidine
Neuroectodermal Tumors
Neuroectodermal Tumors, Primitive
Neuroectodermal Tumors, Primitive, Peripheral
Neoplasms, Neuroepithelial
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Radiopharmaceuticals