Phase I/II multicenter study to assess efficacy and safety of ribociclib (LEE011) in combination with topotecan and temozolomide (TOTEM) in pediatric patients with relapsed or refractory neuroblastoma and other solid tumors

ovartis Pharma AG0 sites230 target enrollmentFebruary 27, 2023

Overview

No summary available.

Registry

who.int

Start Date

February 27, 2023

End Date

TBD

Last Updated

2 years ago

Study Type

Interventional clinical trial of medicinal product

Sex

All

Sponsor

•1\.Signed informed consent/assent must be obtained prior to participation in the study. Participants and/or guardian must have the ability to understand and the willingness to sign a written informed consent document.
•2\.Age \= 12 months and \= 21 years at the time of signing consent form.
•3\.Histologically or cytologically confirmed solid tumors listed below that have progressed despite standard therapy or for which no effective standard therapy exists.
•a. Neuroblastoma (NB) (Phase I and Phase II)
•i. Histologically proven NB as per International Neuroblastoma Staging System (INSS)
•ii. Relapsed: any relapsed or progressed high\-risk (HR)\-NB
•iii. Refractory high\-risk disease: lack of adequate response to frontline therapy that precludes the participant from proceeding to consolidation therapies (e.g. myeloblative chemotherapy)
•iv. Measurable disease by cross sectional imaging and/or evaluable disease (uptake on MIBG scan or FDG PET with or without bone marrow histology) per International Neuroblastoma Response Criteria (INRC).
•v. Imaging confirmed disease recurrence or progression
•vi. Participants must have an available MYCN amplification status before screening.

•1\. Known hypersensitivity to any of the excipients of ribociclib or topotecan or temozolomide.
•2\. Not recovered from clinical and laboratory acute toxicities related to prior anti\-cancer therapies.
•3\. Concurrent severe and/or uncontrolled concurrent medical conditions that in the Investigator's judgement could compromise their ability to tolerate or absorb protocol therapy or would interfere with the study procedures or results.
•4\. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.
•5\. History of QTcF prolongation (i.e. QTcF interval of \> 450 ms) or QTcF \> 450 ms on screening ECG.
•6\. Currently taking medications with a known risk to prolong the QT interval or induce TdP that cannot be discontinued or replaced by safe alternative medication.
•7\. Currently taking medications that are known strong inducers or inhibitors of CYP3A4/5 cannot be discontinued at least 7 days or 5 half\-lives.
•8\. Currently taking medications that are mainly metabolized by CYP3A4/5 with a narrow therapeutic index that cannot be discontinued at least 7 days or 5 half\-lives.
•9\. Vaccinated with live, attenuated vaccines within 4 weeks.
•10\. Participated in a investigational study within 30 days or 5 half\-lives.