NCT05952687

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

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• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 6 Months – 25 Years
• Healthy volunteers: Not accepted

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

Detailed 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.

Conditions

• Rhabdoid Tumor
• Atypical Teratoid/Rhabdoid Tumor
• Atypical Teratoid/Rhabdoid Tumor of CNS
• CNS Tumor

Interventions

Type	Name	Description
DRUG	Idasanutlin	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 using single agent idasanutlin.
DRUG	Idasanutlin	Patients will receive idasanutlin dosed once daily on Days 1-5 of a 28-day cycle starting with the RP2D determined in the dose-finding/safety phase.
DRUG	Selinexor	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.

Timeline

• Start date: 2024-03-01
• Primary completion: 2025-09-01
• Completion: 2032-08-01
• First posted: 2023-07-19
• Last updated: 2024-03-27

Regulatory

• FDA-regulated drug study