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

NCT ID: NCT03561259

Last Updated: 2023-02-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-21

Study Completion Date

2025-04-30

Brief Summary

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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

Detailed Description

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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.

Conditions

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Neuroblastoma Neuroectodermal Tumors Neoplasms

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Two-arm, non-randomized, open-label study.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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131I-MIBG

131I-MIBG

Group Type EXPERIMENTAL

131I-MIBG

Intervention Type DRUG

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.

131I-MIBG + Vorinostat

131I-MIBG + Vorinostat

Group Type EXPERIMENTAL

131-MIBG + Vorinostat

Intervention Type DRUG

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.

Interventions

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131I-MIBG

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.

Intervention Type DRUG

131-MIBG + Vorinostat

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.

Intervention Type DRUG

Other Intervention Names

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I-131 meta-iodobenzylguanidine Iobenguane I-131 MIBG Injection

Eligibility Criteria

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Inclusion Criteria

1. 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.
2. May have had prior 131I-MIBG therapy, provided:

1. It has been at least 6 months from the date of last 131I-MIBG ;
2. Response was other than progressive disease on first restaging after 131I-MIBG ;
3. Prior 131I-MIBG was given as monotherapy and not in combination with systemic anticancer agents;
4. Cumulative lifetime dose of 131I-MIBG at enrollment does not exceed 18 mCi/kg.
3. All soft tissue lesions identified on CT/MRI scans must be iobenguane avid lesions on an (123I)-iobenguane scan, or

1. any progressive non-iobenguane avid lesion is proven by biopsy to be a non-neuroblastoma lesion.
2. any other non-avid lesion is comprised of a fibrotic or scarred mass as shown by routine imaging and confirmed by the investigator.
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 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.
6. 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.
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 ≤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).
12. 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.
13. 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).
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.
16. Coagulation Function:

1. International Normalized Ratio (INR) \< 1.5
2. Partial thromboplastin time (PTT) \< 1.5 times upper limit of normal.

Exclusion Criteria

1. Subjects within 5 half-lives after any antibody-based immunotherapy, or have not recovered 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 4 months 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 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)
5. History of total body irradiation.
6. 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
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 not required prior to study entry).
10. Clinically important cardiac, pulmonary, and hepatic impairment.

1. Since valproic acid has HDAC inhibitory activity, patients must not have received valproic acid within 30 days of study entry.
2. 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.
3. Patients with a history of deep venous thrombosis that was not associated with the presence of a central venous catheter.
4. Patients who are receiving Coumadin.
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Jubilant DraxImage Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Melda Dolan

Role: STUDY_DIRECTOR

Jubilant DraxImage Inc., dba Jubilant Radiopharma

Locations

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Stanford University

Palo Alto, California, United States

Site Status NOT_YET_RECRUITING

UCSF Pediatric Hematology/Oncology

San Francisco, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Nemours Children's Specialty Care

Jacksonville, Florida, United States

Site Status RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

University of Minnesota

Minneapolis, Minnesota, United States

Site Status RECRUITING

Washington University Medical Center in St. Louis

St Louis, Missouri, United States

Site Status RECRUITING

Northwell Health /Cohen Children's Medical Center

New Hyde Park, New York, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

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

Charlotte, North Carolina, United States

Site Status RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

University of Texas Southwestern Medical Center, Children's Health

Dallas, Texas, United States

Site Status RECRUITING

Cook Children's Hematology/Oncology Center

Fort Worth, Texas, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status RECRUITING

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

Madison, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Melda Dolan, MD

Role: CONTACT

1-215-930-4550

Suzanne Bissonnette

Role: CONTACT

215-406-0127

Facility Contacts

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Elizabeth Reichert, PhD

Role: primary

650-724-8842

Debbie Lara

Role: primary

415-476-2218

Astrid Eder

Role: primary

720-777-8531

Manisha M Bansal, MD

Role: primary

904-697-3793

Melissa Z Marx, MPH

Role: primary

773-702-2927

Roxane Mitten

Role: primary

319-356-1212

Catherine M Clinton, MS

Role: primary

617-632-5556

Ashley Schempp, MPH

Role: primary

612-625-9340

Sally Jones, MA, CCRP

Role: primary

314-454-4353

Eva Atsidaftos

Role: primary

Yusuf Sattar

Role: backup

Ellen M Basu, MD, PhD

Role: primary

212-639-5204

Katherine Farmer

Role: primary

704-641-7350

Lori Backus

Role: primary

513-636-2047

Yael Mosse, MD

Role: primary

215-590-0965

Jennifer Saggio

Role: backup

Doreen Snelsire

Role: primary

412-692-8864

Doreen Snelsire

Role: primary

Beverly Kleiber, PhD, CCRP

Role: primary

214-456-1003

Juli Ramirez

Role: primary

682-885-2580

Akudo Anyanwu:

Role: primary

832-824-4167

Christine Goetz, BA,CCRC

Role: primary

206-884-1149

Jenny Weiland

Role: primary

608-890-8070

Celeste Matsuchima

Role: backup

608-890-8069

Other Identifiers

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MIBG 2014-01

Identifier Type: -

Identifier Source: org_study_id

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