NCT05429502

Study of 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

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

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Novartis Pharmaceuticals · Industry
• Sex: All
• Age: 12 Months – 21 Years
• Healthy volunteers: Not accepted

Summary

This is a Phase I/II study to assess the efficacy and safety of ribociclib in combination with topotecan and temozolomide (TOTEM) in pediatric patients with relapsed or refractory (r/r) neuroblastoma (NB), and other solid tumors, including medulloblastoma (MB), high-grade glioma (HGG), malignant rhabdoid tumors (MRT), and rhabdomyosarcoma (RMS).

Detailed description

The study is structured into two parts: Phase I - Part A (dose finding) and Phase I - Part B (multiple expansion cohorts). Phase II may commence following the evaluation of Phase I data, which includes safety, tolerability, efficacy, pharmacokinetics, and biomarker data. Additionally, other emerging data that could influence the treatment landscape will be considered before initiating Phase II in patients with relapsed or refractory neuroblastoma (NB) and/or other tumors studied in Phase I. \- Phase I - Part A (dose finding): This phase aims to determine the maximum tolerated dose (MTD) and/or the recommended Phase II dose (RP2D) of ribociclib in combination with TOTEM. Due to the early termination of the trial, Phase I - Part B (multiple expansion cohorts) and Phase II (double-blind, randomized, placebo-controlled in relapsed or refractory NB) were not initiated.

Conditions

• Neuroblastoma

Interventions

Type	Name	Description
DRUG	Topotecan	Starting out dose of topotecan administered at standard dose given to neuroblastoma patients (0.75 mg/m2/day).
DRUG	Temozolomide	Starting out dose of temozolomide for cohort A1 and A2 for Phase 1-Part A: 150mg/m2/day. Starting out dose for subsequent cohorts, Cohort A3 and onwards, in Phase 1-Part A will initiate at 100mg/m2/day.
DRUG	Ribociclib	Starting out dose of ribociclib for cohort A1 Phase 1-Part A: 200mg/m2/day. Starting out dose for Cohort A2 and A3 was 100mg/m2/day.

Timeline

• Start date: 2022-12-27
• Primary completion: 2025-02-26
• Completion: 2025-02-26
• First posted: 2022-06-23
• Last updated: 2025-10-10

Locations

6 sites across 4 countries: United States, Germany, Italy, United Kingdom

Regulatory

• FDA-regulated drug study