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NeuroblastomaPhase 2OPTIMUMNCT03561259

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

A Phase 2 study testing 131I-MIBG and 131-MIBG + Vorinostat in people with Neuroblastoma and Neuroectodermal Tumors, run by Jubilant DraxImage Inc. at 21 sites in United States.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 1 year and older
Conditions the study is for
Neuroblastoma, Neuroectodermal Tumors, Neoplasms
What is being tested?
131I-MIBG and 131-MIBG + Vorinostat
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
21 sitesUnited States
Study dates
21 Oct 2019to Apr 2025
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Subjects with a diagnosis of iobenguane avid, high-risk neuroblastoma based on Revised INRC criteria at the time of study enrollment with recurrent or progressive disease at any time prior to enrollment, 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.
  • May have had prior 131I-MIBG therapy, provided:
  • It has been at least 6 months from the date of last 131I-MIBG ;
  • Response was other than progressive disease on first restaging after 131I-MIBG ;
  • Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents;
  • Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
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  • All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or
  • any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion.
  • any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator.
  • 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).
  • If a male, 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.
  • If a female 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.
  • Age at study entry ≥1 year.
  • 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.
  • Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline.
  • An absolute neutrophil count ≥750/μL without growth factor for 5 days.
  • Liver function parameter results: total bilirubin ≤2 × upper limit of normal for age, and Serum alanine aminotransferase (glutamic-pyruvic transaminase) and serum aspartate aminotransferase (glutamic-oxaloacetic transaminase) ≤ 10 times the upper limit of normal (for all sites, the upper limit of normal for alanine aminotransferase is defined as 45 U/L).
  • Normal thyroid function as measured by T4 or TSH or have abnormal results that are not considered clinically important by the Investigator or may be receiving levothyroxine.
  • Cardiac Function: shortening fraction of ≥ 27% by echocardiogram or ejection fraction ≥ 50% documented by echocardiogram or radionuclide angiogram within 1 month prior to Visit 1 (Baseline).
  • 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%.
  • Full recovery from the toxic effects of any prior therapy.
  • Coagulation Function:
  • International Normalized Ratio (INR) < 1.5
  • Partial thromboplastin time (PTT) < 1.5 times upper limit of normal.

Who cannot join

  • Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered from effects of any biologic therapy.
  • Subjects <12 weeks after myeloablative therapy with autologous stem cell transplant.
  • 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.
  • Subjects must not have received radiation for a minimum of 2 weeks prior to study enrollment. Subjects whose only site(s) of disease have been radiated are eligible as long as the subject has MIBG avidity 2 weeks after completion of radiation. A minimum of 12 weeks prior to study enrollment is required following prior large field radiation therapy (ie, craniospinal, whole abdominal, total lung, > 50% marrow space)
  • History of total body irradiation.
  • Subjects do not have adequate renal function defined as GFR ≥ 70 mL/min/1.73 m2 either by creatinine clearance or radioisotope direct measurement or by calculation with the Schwartz formula
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  • Subjects who are on hemodialysis.
  • Pregnancy or breastfeeding.
  • 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).
  • Clinically important cardiac, pulmonary, and hepatic impairment.
  • Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
  • Since valproic acid has HDAC inhibitory activity, patients must not have received valproic acid within 30 days of study entry.
  • Since vorinostat may prolong the QT interval, patients must not be receiving other 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.
  • Patients with a history of deep venous thrombosis that was not associated with the presence of a central venous catheter.
  • Patients who are receiving Coumadin.

Trial locations and contacts

21 sites in 1 country.

Melda Dolan, MD contact

1-215-930-4550

melda.dolan@jubl.com

Suzanne Bissonnette contact

215-406-0127

SBissonnette@jubl.com

21 sites in 1 country

United States21 sites, 21 recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Astrid Eder, 720-777-8531, astrid.eder@coloradochildrens.org

    Margaret Macy, MD

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Catherine M Clinton, MS, 617-632-5556, Catherine_clinton@dfci.harvard.edu

    Suzanne Shusterman, MD

    Recruiting

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

    Charlotte, North Carolina, 28203

    Katherine Farmer, 704-641-7350, Katherine.Farmer@atriumhealth.org

    Javier E Osterheld, MD

    Recruiting

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

    Melissa Z Marx, MPH, 773-702-2927, lzeilner@peds.bsd.uchicago.edu

    Ami V Desai, MD

    Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

    Lori Backus, 513-636-2047, lori.backus@cchmc.org

    Brian Weiss, MD

    Recruiting

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

    Dallas, Texas, 75235

    Beverly Kleiber, PhD, CCRP, 214-456-1003, beverly.kleiber@childrens.com

    Tanya Watt, MD

    Recruiting

  • Cook Children's Hematology/Oncology Center

    Fort Worth, Texas, 76104

    Juli Ramirez, 682-885-2580, juli.ramirez@cookchildrens.org

    Meaghan Granger, MD

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77030

    Akudo Anyanwu:, 832-824-4167, aanyanw@texaschildrens.org

    Jennifer Foster, MD

    Recruiting

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

    Roxane Mitten, 319-356-1212, roxanne-mitten@uiowa.edu

    David Dickens, MD

    Recruiting

  • Nemours Children's Specialty Care

    Jacksonville, Florida, 32207

    Manisha M Bansal, MD, 904-697-3793, Manisha.Bansal@nemours.org

    Manisha Bansal, MD

    Recruiting

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

    Madison, Wisconsin, 53792

    Jenny Weiland, 608-890-8070, jlweiland@pediatrics.wisc.edu

    Celeste Matsuchima, 608-890-8069, camatsus@pediatrics.wisc.edu

    Recruiting

  • University of Minnesota

    Minneapolis, Minnesota, 55455

    Ashley Schempp, MPH, 612-625-9340, john3587@umn.edu

    Emily Greengard, MD

    Recruiting

  • Northwell Health /Cohen Children's Medical Center

    New Hyde Park, New York, 11040

    Eva Atsidaftos, eatsidaf@northwell.edu

    Yusuf Sattar, YSattar@northwell.edu

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Ellen M Basu, MD, PhD, 212-639-5204

    Ellen Basu, MD, PhD

    Recruiting

  • Stanford University

    Palo Alto, California, 94304

    Elizabeth Reichert, PhD, 650-724-8842, lreichert@stanford.edu

    Robbie Majzner, MD

    Not yet recruiting

  • The Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Yael Mosse, MD, 215-590-0965, mosse@email.chop.edu

    Jennifer Saggio, SAGGIO@email.chop.edu

    Recruiting

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

    Doreen Snelsire, 412-692-8864, Doreen.Snelsire@chp.edu

    Andrew Bukowinski, MD

    Recruiting

  • UPMC Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15224

    Doreen Snelsire, Doreen.Snelsire@chp.edu

    Andrew Bukowinski, MD

    Recruiting

  • UCSF Pediatric Hematology/Oncology

    San Francisco, California, 94158

    Debbie Lara, 415-476-2218, Debbie.deLara@ucsf.edu

    Kieuhoa Vo, MD

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Christine Goetz, BA,CCRC, 206-884-1149, christine.goetz@seattlechildrens.org

    Navin R Pinto, MD

    Recruiting

  • Washington University Medical Center in St. Louis

    St Louis, Missouri, 63110

    Sally Jones, MA, CCRP, 314-454-4353, jones_s@wustl.edu

    Frederick Huang, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase II, Open Label, Two-Arm Study of Therapeutic Iobenguane (131I) as Single Agent or in Combination With Vorinostat for Recurrent or Progressive High- Risk Neuroblastoma Subjects (OPTIMUM TRIAL)

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

Read the detailed 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.

Being tested
131I-MIBG, 131-MIBG + Vorinostat
Keywords
Iobenguane Avid High-risk Neuroblastoma, 3-Iodobenzylguanidine, Radiopharmaceutical
Medical subject headings
Neuroblastoma, Neuroectodermal Tumors, Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 131I-MIBGDrug

    Also called I-131 meta-iodobenzylguanidine, Iobenguane I-131 MIBG Injection

    Subjects will receive 18 mCi/kg of 131I-MIBG administered over 1.5 to 2 hours on Day 1 either a central line or a peripheral intravenous catheter. The maximum absolute dose of 131I-MIBG 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 protocol predefined criteria, may receive a second 18 mCi/kg 131I-MIBG treatment no sooner than 6 weeks following the first treatment.

  • 131-MIBG + VorinostatDrug

    Subjects will receive vorinostat 180 mg/m2/dose (maximum dose 400 mg) once daily by mouth, NG, or G-tube on days -1 to +12 (14 total doses) for 14 days continuously. The 131I-MIBG treatment will be administered on day 1 via either a central line or a peripheral intravenous catheter over 1.5 to 2 hours. On day 1 of therapy, vorinostat should be taken 1 hour prior to the start of the 131I-MIBG infusion. 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 course of 18 mCi/kg 131I-MIBG combined with vorinostat (180 mg/m2) no sooner than 6 weeks following the first therapeutic 131I-MIBG treatment.

Study groups in NCT03561259
Study groupRoleWhat they receive
131I-MIBGExperimental131I-MIBG
Receives: Drug: 131I-MIBG
131I-MIBG + VorinostatExperimental131I-MIBG + Vorinostat
Receives: Drug: 131-MIBG + Vorinostat

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response

    Overall response (Yes/No) is based on the International Neuroblastoma Response Criteria (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.

    Measured: 6 weeks after the last 131I-MIBG treatment which will either be the first or the second treatment course (131I-MIBG + vorinostat) and a confirmatory assessment at least 6 weeks thereafter (at least 12 weeks from the end of treatment)

Secondary outcomes (4)

  1. Overall Response at 6 weeks after 131I-MIBG treatment

    The Revised INRC overall response (yes/no) defined as complete response, partial response, or minor response 6 weeks after the last131I-MIBG treatment which will either be the first treatment or the second treatment.

    Measured: 6 weeks after the last 131I-MIBG treatment (first or second treatment of 131I-MIBG + vorinostat).

  2. Durability of Effect of Overall Response (Yes/No)

    Durability of effect with the INRC will be assessed as INRC for all tumor assessment data available including any data collected beyond 12 weeks after the last 131I-MIBG treatment which will either be the first treatment or the second treatment.

    Measured: For all tumour assessment data collected throughout the study (up to the end of the 2-year follow-up)(131I-MIBG + vorinostat).

  3. Relative Curie Extension Score

    Relative Curie Extension Score 6 weeks after the last MIBG 131I treatment, which will either be the first treatment or the second treatment.

    Measured: 6 weeks after the last 131I-MIBG treatment which will either be the first or the second treatment course (131I-MIBG + vorinostat)

  4. Durability of Effect of Relative Curie Extension Score

    Durability of effect with the Relative Curie Extension Score will be assessed as the score for all tumor assessment data available including any data collected beyond 12 weeks after the last MIBG 131I treatment, which will either be the first treatment or the second treatment. The Relative Curie Extension Score will be calculated using the Baseline (Visit 2) Absolute Curie Extension Score. The Curie Extension Scores will be calculated from the results of the (123I) iobenguane scans.

    Measured: For all tumour assessment data collected throughout the study for both arms (up to the end of the 2-year follow-up).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jun 2018
  2. Study start21 Oct 2019
  3. Primary completion1 Dec 2023 (estimated)
  4. Study completionApr 2025 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Model description
Two-arm, non-randomized, open-label study.
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03561259
Sponsor's protocol ID
MIBG 2014-01
Acronym
OPTIMUM
Status last verified
Feb 2023
First submitted
7 Jun 2018
Last updated
16 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing 131I-MIBG and 131-MIBG + Vorinostat in people with Neuroblastoma and Neuroectodermal Tumors, run by Jubilant DraxImage Inc. at 21 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 24 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 16 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Melda Dolan, MD (1-215-930-4550, melda.dolan@jubl.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Response (time frame: 6 weeks after the last 131I-MIBG treatment which will either be the first or the second treatment course (131I-MIBG + vorinostat) and a confirmatory assessment at least 6 weeks thereafter (at least 12 weeks from the end of treatment)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03561259.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2023.

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