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

Sponsor
St. Jude Children's Research Hospital
Study ID
NCT05952687
Phase
PHASE1
Status
Withdrawn

Conditions

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

Eligibility Criteria

Sex
ALL
Age
6 Months - 25 Years
Healthy Volunteers
Not accepted

Interventions

  • Idasanutlin — DRUG
    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.
  • Idasanutlin — DRUG
    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.
  • Selinexor — DRUG
    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.

Study Details

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

Key Dates

Start date
Mar 31, 2024
Status verified
Mar 2024
Primary completion
Sep 30, 2025
Completion
Aug 31, 2032

Study Design

Enrollment
0 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Dose Finding/Safety Phase
    Patients with progressive/relapsed atypical teratoid/rhabdoid tumors (AT/RT) \& malignant rhabdoid tumors (MRT) or synchronous/metachronous AT/RT \&MRT
  • Experimental: Expansion Phase: Stratum A
    Patients with progressive/relapsed AT/RT
  • Experimental: Expansion Phase: Stratum B
    Patients with progressive/relapsed MRT
  • Experimental: Expansion Phase: Stratum C
    Patients with progressive/relapsed, synchronous/metachronous AT/RT \& MRT

Primary Outcome Measure

Maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of combination treatment with oral idasanutlin and selinexor in children with recurrent or progressive AT/RT or MRT in the dose finding/safety phase. [ Time Frame: 1 month after start of idasanutlin and selinexor treatment ]

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