Phase I Study of Investigational Medicinal Products in Children With Relapsed/Refractory Neuroblastoma (Inbraced)
|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: NCT02914405|
Recruitment Status : Recruiting
First Posted : September 26, 2016
Last Update Posted : July 8, 2019
Neuroblastoma, the most common extra-cranial solid tumour in children, remains one of the major challenges in paediatric oncology. A promising way to further improve outcome in this disease appears to be the development of adjuvant therapeutic strategies. In this research the anti-GD2 antibody, which is a standard treatment, is to be combined with 131-l Metaiodobenzylguanidine (mlBG) and anti-Programmed Cell Death Protein 1 (anti-PD1) antibody Nivolumab - the investigated drugs - with the aim of generating sustained anti-neuroblastoma immunity. In particular it will be determined the safety and tolerability of the novel combination as well as documented any evidence of efficacy in paediatric patients with relapsed and refractory high risk neuroblastoma.
This study is sponsored by the University Hospital Southampton and will take place in 4 hospitals in the United Kingdom, Germany and USA. The estimated duration of the study is 2 years, starting in December 2016.
This is an "adaptive study". Such design uses accumulating of data from the ongoing trial to modify aspects of the study (e.g. duration, number of treatments) without undermining its validity or integrity. There will be 3 cohorts of patients. As safety of Nivolumab is well established, Cohort 1 will assess its safety and tolerability in combination with 131-l mlBG. Cohort 2 will then add anti-GD2 to the drug combination, assessing safety and tolerability. Cohort 3 will escalate all 3 agents to the full 100% dose level to assure safety for expanded analyses of clinical and laboratory data at that dose level.
Patients will initially be recruited into Cohort 1. Patients must have completed at least 12 weeks of trial treatment without reaching a Dose Limiting Toxicity before a patient can be recruited to the next cohort.
A minimum of 3 evaluable patients will be treated in cohorts 1-3. Assuming the full dose combination therapy (cohort) is tolerable, 15 evaluable patients will be treated.
|Condition or disease||Intervention/treatment||Phase|
|Neuroblastoma||Drug: Nivolumab Drug: Ch14.18/CHO||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||36 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of 131-1 Meta-iodobenzylguanidine (mIBG) Followed by Nivolumab and Chimeric 14.18 Anti-GD2 Monoclonal Antibody Produced in Chinese Hamster Ovary Cells (ch14.18/CHO) in Children With Relapsed/Refractory Neuroblastoma|
|Actual Study Start Date :||May 24, 2018|
|Estimated Primary Completion Date :||May 2020|
|Estimated Study Completion Date :||May 2020|
The dose and schedule of 131-I mIBG will be constant, and the doses of ch14.18/ CHO and Nivolumab determined by cohort:
Nivolumab is a soluble protein consisting of 4 polypeptide chains, which include 2 identical heavy chains consisting of 440 amino acids and 2 identical light chains. Molecular weight is 146,221 daltons.
APN311 (ch14.18/CHO) is manufactured in a Good Manufacturing Practice (GMP) compliant facility of Polymun Scientific, Austria according to a state of the art aseptic manufacturing process based on a characterized and stable Chinese Hamster Ovary (CHO) cell line. After propagation of the working cell bank (WCB) in small volume vessels/bioreactors, manufacture is carried out in a 2500 L stirred tank reactor utilizing components which are free of material of animal or human origin.
Other Name: Mouse-human chimeric monoclonal anti-GD2 Immunoglobulin G1 (IgG1) antibody
- Incidence of Treatment-Emergent Adverse Events [Safety and tolerability] of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients [ Time Frame: 2 Years ]• To determine the safety and tolerability of the novel combination of 131-I-MIBG, ch14.18/CHO and Nivolumab in paediatric patients, assessed by nature, frequency, severity and timing of adverse events, including serious adverse events and immune related adverse events during administration of ch14.18/CHO
- Anti-tumour response in patients with measureable disease as measured by immunocytology, MIBG, CT and/or MRI in patients receiving 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma [ Time Frame: 2 Years ]To document any evidence of efficacy of 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma (time to progression)
- Anti-tumour response in patients with measureable disease as measured by immunocytology, MIBG, CT and/or MRI in patients receiving 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma [ Time Frame: 2 Years ]To document any evidence of efficacy of 131-I-MIBG, ch14.18/CHO and Nivolumab in patients with relapsed and refractory high risk neuroblastoma (objective response rate)
- KIR/KIR-Ligand genotype, FcγR genotype [ Time Frame: 2 Years ]To provide descriptive analysis of any associations between KIR/KIR-Ligand genotype, FcγR genotype and response
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): NCT02914405
|Contact: Danny Pratt||+44(0)2381204989 ext email@example.com|
|University Hospital Southampton NHS Foundation Trust||Recruiting|
|Southampton, Hampshire, United Kingdom, SO16 6YD|
|Contact: Danny B Pratt 023 8120 4989 ext 3943 firstname.lastname@example.org|
|Contact: Tom Bower 023 8120 4989 ext 3853 email@example.com|
|Principal Investigator: Juliet C Gray|
|University College London Hospital||Recruiting|
|London, United Kingdom, NW1 2BU|
|Contact: Pamela Niem 023 447 7135 Pamela.Niem@nhs.net|
|Contact: Sarah Taylor 07890 60 9229 firstname.lastname@example.org|
|Principal Investigator: Mark Gaze|
|Principal Investigator:||Juliet Gray||Consultant Paediatric Oncologist|