Trial of Idasanutlin and Selinexor Therapy for Children With Progressive/Relapsed AT/RT or Extra-CNS Malignant Rhabdoid Tumors

Rhabdoid Tumor Clinical Trial

Official title: iSTAR: Phase 1b Trial of Idasanutlin and Selinexor Therapy For Children With Progressive/Relapsed Atypical Teratoid Rhabdoid Tumors, Extra-CNS Malignant Rhabdoid Tumors Or Synchronous/Metachronous Rhabdoid Tumors

Status Withdrawn

Clinical Trial Summary

iSTAR is an open-label, multi-center, phase 1b study of oral XPO1 inhibitor selinexor and oral MDM2 inhibitor idasanutlin in children with progressive or recurrent atypical teratoid/rhabdoid tumors (AT/RT), malignant rhabdoid tumors (MRT) and synchronous/metachronous rhabdoid tumors.

Primary Objectives

• To determine the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D) of combination treatment with oral idasanutlin and selinexor in children with recurrent or progressive AT/RT or MRT.

• To characterize the plasma pharmacokinetics of oral idasanutlin and selinexor in children with recurrent or progressive AT/RT or MRT, to assess potential covariates to explain the inter- and intra-individual pharmacokinetic variability.

Secondary Objectives

• Evaluate safety of the combination treatment with oral idasanutlin and selinexor in children

• Evaluate efficacy of the combination treatment of idasanutlin and selinexor as measured by objective response (partial response [PR] or complete response [CR]) rate separately in progressive/relapsed AT/RT and progressive/relapsed MRT

• Estimate progression-free and overall-survival separately in progressive/relapsed AT/RT and progressive/relapsed MRT

Clinical Trial Description

Patients will receive idasanutlin dosed once daily on Days 1-5 of a 28-day cycle starting with 80% of the RP2D determined in the ongoing pediatric iMATRIX trial (NCT04029688) using single agent idasanutlin. Patients will receive selinexor on Day 4 of each of the first 3 weeks of a 28-day cycle. Selinexor will be skipped on week 4 of each cycle.

The dose-finding/safety phase will test two dosing frequencies and two dose levels of selinexor [100, and 75% of the RP2D from the COG trial (NCT02323880)] using single agent selinexor and 2 dose levels of idasanutlin [80% and 100% of the RP2D from the pediatric single agent idasanutlin iMATRIX study (NCT04029688)]. In the COG trial, ADVL1414, the RP2D of single agent selinexor was 35mg/m2 administered weekly of a 28-day cycle without any break. In our trial we propose to skip selinexor during week 4 (dose levels 1). If unexpected toxicity is encountered in dose level 1, St. Jude will open dose level -1(reduced frequency of selinexor dosing) and dose level -2 (reduced dose and frequency of selinexor dosing). However, if dose level 1 is well tolerated, then the St. Jude will open dose level 2 for enrollment (100% of RP2D of single agent selinexor and idasanutlin).

Once the RP2D is established, patients enrolled on the dose-finding/safety phase at this dose level will continue treatment and will be included in the response analysis in the expansion stage. Those patients who are enrolled on the dose-finding/safety phase at a lower dose level and are still on treatment will have their doses optimized following determination of the RP2D. Patients may continue treatment for a maximum of 2 years, or 26 cycles, in absence of progressive disease. ;

Related Conditions & MeSH terms

• Atypical Teratoid/Rhabdoid Tumor
• CNS Tumor
• Neoplasms
• Rhabdoid Tumor

• NCT number: NCT05952687
• Study type: Interventional
• Source: St. Jude Children's Research Hospital
• Status: Withdrawn
• Phase: Phase 1
• Start date: March 2024
• Completion date: August 2032