Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumours, Including Central Nervous System Tumours

Official Title

A Phase 1/2 Study of Lenvatinib in Combination With Everolimus in Recurrent and Refractory Pediatric Solid Tumours, Including CNS Tumours

Summary:

Phase 1 of this study, utilizing a rolling 6 design, will be conducted to determine a maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), and to describe the toxicities of lenvatinib administered in combination with everolimus once daily to pediatric participants with recurrent/refractory solid tumours. Phase 2, utilizing Simon's optimal 2-stage design, will be conducted to estimate the antitumour activity of lenvatinib in combination with everolimus in pediatric participants with selected recurrent/refractory solid tumours including Ewing sarcoma/peripheral primitive neuroectodermal tumour (pPNET), rhabdomyosarcoma, and high grade glioma (HGG) using objective response rate (ORR) at Week 16 as the outcome measure.

Trial Description

Primary Outcome:

• Maximum tolerated dose (MTD) of lenvatinib in combination with everolimus: Phase 1
• Recommended Phase 2 dose (RP2D) of lenvatinib in combination with everolimus: Phase 1
• Number of participants with any treatment-emergent (TE) serious adverse event (SAE) in Phase 1, as a measure of the safety and toxicity of lenvatinib in combination with everolimus
• Number of participants with any TE adverse event (TEAE) in Phase 1, as a measure of the safety and toxicity of lenvatinib in combination with everolimus
• Overall Response Rate (ORR) at Week 16 for Phase 2

• ORR at the time of data cutoff: Phase 1
• ORR at the time of data cutoff: Phase 2
• Disease Control Rate (DCR): Phase 1
• DCR: Phase 2
• Clinical Benefit Rate (CBR): Phase 1
• CBR: Phase 2
• Duration of Response (DOR): Phase 1
• DOR: Phase 2
• Area under the plasma concentration time course profile (AUC): Phase 1
• AUC: Phase 2
• Maximum observed concentration (Cmax): Phase 1
• Cmax: Phase 2
• Time from dosing to the maximum observed concentration (Tmax): Phase 1
• Tmax: Phase 2
• Number of participants with any TE SAE in Phase 2, as a measure of the safety and toxicity of lenvatinib in combination with everolimus
• Number of participants with any TEAE in Phase 2, as a measure of the safety and toxicity of lenvatinib in combination with everolimus

View this trial on ClinicalTrials.gov