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

  • STATUS
    Recruiting
  • End date
    Apr 24, 2025
  • participants needed
    60
  • sponsor
    Jubilant DraxImage Inc.
Updated on 24 March 2022
platelet count
total bilirubin
stem cell transplantation
cyclophosphamide
busulfan
vincristine
ejection fraction
melphalan
serum pregnancy test
growth factor
karnofsky performance status
bone marrow procedure
shortening fraction
etoposide
doxorubicin
vorinostat
neutrophil count
carboplatin
pulse oximetry
cancer chemotherapy
avid
platelet transfusion
iobenguane
platelet transfusions
ifosfamide
topotecan
mg++
high-risk neuroblastoma

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

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.

Details
Condition Neuroblastoma, Neuroectodermal Tumors, Neoplasms
Treatment 131I-MIBG, 131-MIBG + Vorinostat
Clinical Study IdentifierNCT03561259
SponsorJubilant DraxImage Inc.
Last Modified on24 March 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

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
Subjects must have a minimum pulse oximetry measurement of at least 94% at baseline
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
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
aliquots of 2.0 × 10exp6 CD34/kg at the time of study enrollment)
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
Full recovery from the toxic effects of any prior therapy
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
An absolute neutrophil count ≥750/μL without growth factor for 5 days
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
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)
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%
Coagulation Function
International Normalized Ratio (INR) < 1.5
Partial thromboplastin time (PTT) < 1.5 times upper limit of normal

Exclusion Criteria

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
History of total body irradiation
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)
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)
Clinically important cardiac, pulmonary, and hepatic impairment
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
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
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