RECRUITING

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

Conditions

Neuroblastoma Neuroectodermal Tumors Neoplasms Iobenguane Avid High-risk Neuroblastoma 3-Iodobenzylguanidine Radiopharmaceutical

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

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)

Quick Facts

Study Start:2019-10-21

Study Completion:2025-04

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03561259

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	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. 11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy) 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.

Inclusion Criteria

Exclusion 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.

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.
11. Vorinostat treatment exclusion criteria (subjects, who meet any one of these criteria and otherwise meet eligibility criteria, are still eligible for 131I-MIBG monotherapy)
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.

Contacts and Locations

Study Contact

Melda Dolan, MD

CONTACT

1-215-930-4550

melda.dolan@jubl.com

Suzanne Bissonnette

CONTACT

215-406-0127

SBissonnette@jubl.com

Principal Investigator

Melda Dolan

STUDY_DIRECTOR

Jubilant DraxImage Inc., dba Jubilant Radiopharma

Study Locations (Sites)

Stanford University

Palo Alto, California, 94304

United States

UCSF Pediatric Hematology/Oncology

San Francisco, California, 94158

United States

Children's Hospital Colorado

Aurora, Colorado, 80045

United States

Nemours Children's Specialty Care

Jacksonville, Florida, 32207

United States

University of Chicago Medical Center

Chicago, Illinois, 60637

United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

United States

University of Minnesota

Minneapolis, Minnesota, 55455

United States

Washington University Medical Center in St. Louis

Saint Louis, Missouri, 63110

United States

Northwell Health /Cohen Children's Medical Center

New Hyde Park, New York, 11040

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

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

Charlotte, North Carolina, 28203

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229

United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104

United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224

United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224

United States

University of Texas Southwestern Medical Center, Children's Health

Dallas, Texas, 75235

United States

Cook Children's Hematology/Oncology Center

Fort Worth, Texas, 76104

United States

Texas Children's Hospital

Houston, Texas, 77030

United States

Seattle Children's Hospital

Seattle, Washington, 98105

United States

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

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: Jubilant DraxImage Inc.

Melda Dolan, STUDY_DIRECTOR, Jubilant DraxImage Inc., dba Jubilant Radiopharma

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-10-21

Study Completion Date2025-04

Study Record Updates

Study Start Date2019-10-21

Study Completion Date2025-04

Terms related to this study

Keywords Provided by Researchers

Iobenguane Avid High-risk Neuroblastoma
3-Iodobenzylguanidine
Radiopharmaceutical

Additional Relevant MeSH Terms

Neuroblastoma
Neuroectodermal Tumors
Neoplasms