Ignite Creation Date:
2024-05-06 @ 7:17 PM
Last Modification Date:
2024-10-26 @ 3:03 PM
Study NCT ID:
NCT05952687
Status:
WITHDRAWN
Last Update Posted:
2024-03-27
First Post:
2023-07-11
Brief Title:
Trial of Idasanutlin and Selinexor Therapy for Children With ProgressiveRelapsed ATRT or Extra-CNS Malignant Rhabdoid Tumors
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
iSTAR Phase 1b Trial of Idasanutlin and Selinexor Therapy For Children With ProgressiveRelapsed Atypical Teratoid Rhabdoid Tumors Extra-CNS Malignant Rhabdoid Tumors Or SynchronousMetachronous Rhabdoid Tumors
Status:
WITHDRAWN
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Drug withdrawn by company
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 teratoidrhabdoid tumors ATRT malignant rhabdoid tumors MRT and synchronousmetachronous 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 ATRT or MRT
To characterize the plasma pharmacokinetics of oral idasanutlin and selinexor in children with recurrent or progressive ATRT 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 progressiverelapsed ATRT and progressiverelapsed MRT
Estimate progression-free and overall-survival separately in progressiverelapsed ATRT and progressiverelapsed MRT
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 ATRT or MRT
To characterize the plasma pharmacokinetics of oral idasanutlin and selinexor in children with recurrent or progressive ATRT 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 progressiverelapsed ATRT and progressiverelapsed MRT
Estimate progression-free and overall-survival separately in progressiverelapsed ATRT and progressiverelapsed 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-findingsafety 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 35mgm2 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 -1reduced 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-findingsafety 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-findingsafety 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
The dose-findingsafety 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 35mgm2 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 -1reduced 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-findingsafety 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-findingsafety 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| NCI-2023-05552 | REGISTRY | NCI Clinical Trial Registration Program | None |