A Study of Therapeutic Iobenguane (131-I) and Vorinostat for Recurrent or Progressive High-Risk Neuroblastoma Subjects (OPTIMUM)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03561259|
Recruitment Status : Recruiting
First Posted : June 19, 2018
Last Update Posted : October 4, 2022
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma Neuroectodermal Tumors Neoplasms||Drug: 131I-MIBG Drug: 131-MIBG + Vorinostat||Phase 2|
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Two-arm, non-randomized, open-label study.|
|Masking:||None (Open Label)|
|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)|
|Actual Study Start Date :||October 21, 2019|
|Estimated Primary Completion Date :||December 1, 2022|
|Estimated Study Completion Date :||April 2025|
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.
Experimental: 131I-MIBG + Vorinostat
131I-MIBG + Vorinostat
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.
- 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) ]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.
- Overall Response at 6 weeks after 131I-MIBG treatment [ Time Frame: 6 weeks after the last 131I-MIBG treatment (first or second treatment of 131I-MIBG + vorinostat). ]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.
- Durability of Effect of Overall Response (Yes/No) [ Time Frame: For all tumour assessment data collected throughout the study (up to the end of the 2-year follow-up)(131I-MIBG + vorinostat). ]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.
- Relative Curie Extension Score [ Time Frame: 6 weeks after the last 131I-MIBG treatment which will either be the first or the second treatment course (131I-MIBG + vorinostat) ]Relative Curie Extension Score 6 weeks after the last MIBG 131I treatment, which will either be the first treatment or the second treatment.
- Durability of Effect of Relative Curie Extension Score [ Time Frame: For all tumour assessment data collected throughout the study for both arms (up to the end of the 2-year follow-up). ]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.
- Incidence of Adverse Events (CTCAE Version 5.0) [ Time Frame: Up to 22 weeks ]Adverse events as graded according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
- Incidence of Serious Adverse Events [ Time Frame: Through study completion, up to 2.5 years. ]Percentage of subjects with hematological and nonhematological toxicities. Any relationship between the whole body radiation absorbed dose and nonhematological SAEs will also be assessed;
- Whole Body Radiation Dose [ Time Frame: After each 131I-MIBG treatment for up to 120 hours. ]To assess radiation safety in terms of any potential relationship between the whole body radiation absorbed dose and nonhematological serious adverse events (SAEs)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03561259
|Contact: Melda Dolan, MDemail@example.com|
|Study Director:||Melda Dolan||Jubilant DraxImage Inc., dba Jubilant Radiopharma|