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

NCT03561259 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: MIBG 2014-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 21

Brief 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

Conditions

Neuroblastoma; Neuroectodermal Tumors; Neoplasms

Keywords

Iobenguane Avid High-risk Neuroblastoma; 3-Iodobenzylguanidine; Radiopharmaceutical

Outcome Measures

Primary Outcomes (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.

  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)

• Overall Response at 6 weeks after 131I-MIBG treatment

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

• Durability of Effect of Overall Response (Yes/No)

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

• Relative Curie Extension Score

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

• Durability of Effect of Relative Curie Extension Score

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

Other Outcomes (3)

• Incidence of Adverse Events (CTCAE Version 5.0)

  Up to 22 weeks

• Incidence of Serious Adverse Events

  Through study completion, up to 2.5 years.

• Whole Body Radiation Dose

  After each 131I-MIBG treatment for up to 120 hours.

Study Arms (2)

131I-MIBG

EXPERIMENTAL

131I-MIBG

Drug: 131I-MIBG

131I-MIBG + Vorinostat

EXPERIMENTAL

131I-MIBG + Vorinostat

Drug: 131-MIBG + Vorinostat

Interventions

131I-MIBG 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.

Also known as: I-131 meta-iodobenzylguanidine, Iobenguane I-131 MIBG Injection

131I-MIBG

131-MIBG + Vorinostat 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.

131I-MIBG + Vorinostat

Eligibility Criteria

• Age: 1 Year+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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
• 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.
• 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.

Sponsors & Collaborators

• Jubilant DraxImage Inc.: lead

Study Sites (21)

Stanford University

Palo Alto, California, 94304, United States

NOT YET RECRUITING

UCSF Pediatric Hematology/Oncology

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Nemours Children's Specialty Care

Jacksonville, Florida, 32207, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

Washington University Medical Center in St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

Northwell Health /Cohen Children's Medical Center

New Hyde Park, New York, 11040, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

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

Charlotte, North Carolina, 28203, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

University of Texas Southwestern Medical Center, Children's Health

Dallas, Texas, 75235, United States

RECRUITING

Cook Children's Hematology/Oncology Center

Fort Worth, Texas, 76104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

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

Madison, Wisconsin, 53792, United States

RECRUITING

MeSH Terms

Conditions

Neuroblastoma; Neuroectodermal Tumors; Neoplasms

Interventions

3-Iodobenzylguanidine; Vorinostat

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Melda Dolan

  Jubilant DraxImage Inc., dba Jubilant Radiopharma

  STUDY DIRECTOR

Central Study Contacts

Melda Dolan, MD

CONTACT

1-215-930-4550; melda.dolan@jubl.com

Suzanne Bissonnette

CONTACT

215-406-0127; SBissonnette@jubl.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Model Details: Two-arm, non-randomized, open-label study.

Study Record Dates

• First Submitted: June 7, 2018
• First Posted: June 19, 2018
• Study Start: October 21, 2019
• Primary Completion: December 1, 2023
• Study Completion: April 1, 2025
• Last Updated: February 16, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (21)