Ignite Creation Date:
2024-05-06 @ 4:14 PM
Last Modification Date:
2024-10-26 @ 2:06 PM
Study NCT ID:
NCT04923126
Status:
RECRUITING
Last Update Posted:
2024-04-17
First Post:
2021-05-27
Brief Title:
SJ901 Evaluation of Mirdametinib in Children Adolescents and Young Adults With Low-Grade Glioma
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
SJ901 Phase 12 Evaluation of Single Agent Mirdametinib PD-0325901 a Brain-Penetrant MEK12 Inhibitor for the Treatment of Children Adolescents and Young Adults With Low-Grade Glioma
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is an open-label multi-center Phase 12 study of the brain-penetrant MEK inhibitor mirdametinib PD-0325901 in patients with pediatric low-grade glioma pLGG
Detailed Description:
The objectives of this study are
Phase 1
Primary Objectives
To determine the safety and tolerability and estimate the maximum tolerated dose MTDrecommended phase 2 dose RP2D of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma
To characterize the plasma pharmacokinetics PK of mirdametinib
Phase 2
Cohort 1 Newly diagnosed andor previously untreated except surgery
Primary Objectives
To assess the efficacy defined as the sustained objective response rate a Partial Response PR Major Response andor Complete Response CR sustained over 8 weeks observed over any time on active treatment with mirdametinib in previously untreated patients except surgery with WHO grade I or grade II glioma
To characterize the plasma pharmacokinetics of mirdametinib in children adolescents and young adults with low-grade gliomas
To describe the toxicity profile of mirdametinib in pediatric patients
Secondary Objectives
Estimate the efficacy of mirdametinib as measured by progressive free survival PFS and overall survival OS in patients with previously untreated WHO grade I or grade II glioma
To describe treatment responses Progressive Disease Stable Disease Minor Response Partial Response Major Response and Complete Response observed in previously untreated patients except surgery with WHO grade I or grade II glioma over any time on active treatment with mirdametinib
To characterize and monitor patient neurocognitive function and quality of life in patients while on study
Cohort 2 Recurrent andor Progressive without prior exposure to MEK inhibitors
Primary Objectives
To assess the efficacy defined as the sustained objective response rate a PR Major Response andor CR sustained over 8 weeks observed anytime on active treatment with mirdametinib in patients with recurrent andor progressive WHO grade I or grade II glioma not previously treated with MEK inhibitors
To characterize the plasma pharmacokinetics of mirdametinib in children adolescents and young adults with low-grade gliomas
To describe the toxicity profile of mirdametinib in pediatric patients with recurrent or progressive disease not previously treated with MEK inhibitors
Secondary Objectives
Estimate the efficacy of mirdametinib as measured by PFS and OS in patients with recurrent andor progressive WHO grade I or grade II glioma not previously treated with MEKi
To describe treatment responses Progressive Disease Stable Disease Minor Response Partial Response Major Response and Complete Response observed in patients with recurrent andor progressive WHO grade I or grade II glioma without prior exposure to MEK inhibitors
To characterize and monitor patient neurocognitive function and quality of life in patients while on study
Cohort 3 Re-treatment recurrent andor progressive disease previously treated with a MEK inhibitor
Primary Objectives
To estimate the 1-year disease stabilization rate defined as lack of disease progression for 12 courses of mirdametinib in patients with recurrent andor progressive WHO grade I or grade II glioma who previously received 6 courses MEK inhibitor including mirdametinib and did not progress while on active MEKi therapy cohort 3A
To estimate the 6-month disease stabilization rate defined as lack of disease progression for 6 courses of mirdametinib in patients with recurrent andor progressive WHO grade I or grade II glioma who previously received a MEK inhibitor other than mirdametinib and progressed while on active MEKi therapy cohort 3B
To characterize the plasma pharmacokinetics of mirdametinib in children adolescents and young adults with low-grade gliomas
To describe the toxicity profile of mirdametinib in pediatric patients with recurrent or progressive disease previously treated with MEK inhibitors
Secondary Objectives
Estimate the efficacy of mirdametinib as measured by PFS and OS in patients with recurrent andor progressive WHO grade I or grade II glioma previously treated with MEK inhibitors
To describe treatment responses Progressive Disease Stable Disease Minor Response Partial Response Major Response and Complete Response observed in patients with recurrent andor progressive WHO grade I or grade II glioma previously treated with a MEK inhibitor
To characterize and monitor patient neurocognitive function and quality of life in patients while on study
SJ901 will proceed in two phases Phase 1 will evaluate the safety tolerability and pharmacokinetics of mirdametinib when dosed continuously up to 3 mgm2dose twice daily BID in patients with progressive or recurrent pLGG without prior MEK inhibitor MEKi exposure This phase will identify the maximum tolerated dose MTDrecommended phase 2 dose RP2D and will contain a small expansion cohort before launching phase 2 Phase 2 will utilize the MTDRP2D to evaluate mirdametinib efficacy pharmacokinetics safety and tolerability in broader cohorts of patients with newly diagnosed or progressiverecurrent pLGG - prior MEK inhibitor exposure
In Phase 1 of the study participants with progressive or recurrent pLGG without prior MEKi exposure are eligible and will be enrolled onto a single dose level The Rolling 6 design will be used to estimate the MTDRP2D and to determine the dose limiting toxicities DLTs of the escalating doses Once a candidate MTD or RP2D based on 6 subjects has been determined additional evaluable subjects will be enrolled as part of a Phase 1 expansion cohort in order to better describe the safety and tolerability of the MTDRP2D The data from all subjects treated at the MTDRP2D patients from the dose-findingdose-escalation study plus expansion cohort will also be used to assess the stage I efficacy criteria for cohort 2 as part of the Phase 2 design If these criteria are met cohort 2 sample size will be expanded beyond the interim analysis and the Phase 2 study will be initiated in cohort 1
Mirdametinib will be administered twice daily in cycles of 28 days and may be continued for up to 24 months 26 cycles in the absence of disease progression or unacceptable toxicity Doses will be based on the BSA calculated before each cycle of therapy During the DLT period ie cycle 1 all phase 1 participants including those in the phase 1 expansion cohort will receive mirdametinib in dispersible tablets only Thereafter patients who can swallow capsules may transition to capsules if permitted by their specific dose level
Once the phase 2 is open to enrollment participants from the phase 1 on a dose level that differs from the RP2D may choose to change to the RP2D as long as they have not undergone a dose-reduction for toxicity and if the treating physician and the patientfamily agree it is in the best interest of the patient
In Phase 2 of the study participants will be stratified into 3 disease cohorts
Cohort 1 Patients with Newly Diagnosed Low-Grade Glioma
Cohort 2 Patients with Progressive or Recurrent Low-Grade Glioma without Previous MEKi Exposure
Cohort 3 Patients with Progressive or Recurrent Low-Grade Glioma with Previous MEKi Exposure and
Cohort 3A Previously received 6 or more cycles of MEKi therapy and did not progress on MEKi therapy
Cohort 3B Previously treated with MEKi other than mirdametinib and progressed while on MEKi therapy
Therapy will be administered at RP2D in cycles of 28 days and may be continued for up to 24 months 26 cycles in absence of disease progression or unacceptable toxicity Patients in Cohort 3 with previous exposure to mirdametinib may receive a starting dose lower than the RP2D depending on the dose they tolerated during their previous exposure Phase 2 will utilize both the dispersible tablet and capsule formulations
Phase 1
Primary Objectives
To determine the safety and tolerability and estimate the maximum tolerated dose MTDrecommended phase 2 dose RP2D of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma
To characterize the plasma pharmacokinetics PK of mirdametinib
Phase 2
Cohort 1 Newly diagnosed andor previously untreated except surgery
Primary Objectives
To assess the efficacy defined as the sustained objective response rate a Partial Response PR Major Response andor Complete Response CR sustained over 8 weeks observed over any time on active treatment with mirdametinib in previously untreated patients except surgery with WHO grade I or grade II glioma
To characterize the plasma pharmacokinetics of mirdametinib in children adolescents and young adults with low-grade gliomas
To describe the toxicity profile of mirdametinib in pediatric patients
Secondary Objectives
Estimate the efficacy of mirdametinib as measured by progressive free survival PFS and overall survival OS in patients with previously untreated WHO grade I or grade II glioma
To describe treatment responses Progressive Disease Stable Disease Minor Response Partial Response Major Response and Complete Response observed in previously untreated patients except surgery with WHO grade I or grade II glioma over any time on active treatment with mirdametinib
To characterize and monitor patient neurocognitive function and quality of life in patients while on study
Cohort 2 Recurrent andor Progressive without prior exposure to MEK inhibitors
Primary Objectives
To assess the efficacy defined as the sustained objective response rate a PR Major Response andor CR sustained over 8 weeks observed anytime on active treatment with mirdametinib in patients with recurrent andor progressive WHO grade I or grade II glioma not previously treated with MEK inhibitors
To characterize the plasma pharmacokinetics of mirdametinib in children adolescents and young adults with low-grade gliomas
To describe the toxicity profile of mirdametinib in pediatric patients with recurrent or progressive disease not previously treated with MEK inhibitors
Secondary Objectives
Estimate the efficacy of mirdametinib as measured by PFS and OS in patients with recurrent andor progressive WHO grade I or grade II glioma not previously treated with MEKi
To describe treatment responses Progressive Disease Stable Disease Minor Response Partial Response Major Response and Complete Response observed in patients with recurrent andor progressive WHO grade I or grade II glioma without prior exposure to MEK inhibitors
To characterize and monitor patient neurocognitive function and quality of life in patients while on study
Cohort 3 Re-treatment recurrent andor progressive disease previously treated with a MEK inhibitor
Primary Objectives
To estimate the 1-year disease stabilization rate defined as lack of disease progression for 12 courses of mirdametinib in patients with recurrent andor progressive WHO grade I or grade II glioma who previously received 6 courses MEK inhibitor including mirdametinib and did not progress while on active MEKi therapy cohort 3A
To estimate the 6-month disease stabilization rate defined as lack of disease progression for 6 courses of mirdametinib in patients with recurrent andor progressive WHO grade I or grade II glioma who previously received a MEK inhibitor other than mirdametinib and progressed while on active MEKi therapy cohort 3B
To characterize the plasma pharmacokinetics of mirdametinib in children adolescents and young adults with low-grade gliomas
To describe the toxicity profile of mirdametinib in pediatric patients with recurrent or progressive disease previously treated with MEK inhibitors
Secondary Objectives
Estimate the efficacy of mirdametinib as measured by PFS and OS in patients with recurrent andor progressive WHO grade I or grade II glioma previously treated with MEK inhibitors
To describe treatment responses Progressive Disease Stable Disease Minor Response Partial Response Major Response and Complete Response observed in patients with recurrent andor progressive WHO grade I or grade II glioma previously treated with a MEK inhibitor
To characterize and monitor patient neurocognitive function and quality of life in patients while on study
SJ901 will proceed in two phases Phase 1 will evaluate the safety tolerability and pharmacokinetics of mirdametinib when dosed continuously up to 3 mgm2dose twice daily BID in patients with progressive or recurrent pLGG without prior MEK inhibitor MEKi exposure This phase will identify the maximum tolerated dose MTDrecommended phase 2 dose RP2D and will contain a small expansion cohort before launching phase 2 Phase 2 will utilize the MTDRP2D to evaluate mirdametinib efficacy pharmacokinetics safety and tolerability in broader cohorts of patients with newly diagnosed or progressiverecurrent pLGG - prior MEK inhibitor exposure
In Phase 1 of the study participants with progressive or recurrent pLGG without prior MEKi exposure are eligible and will be enrolled onto a single dose level The Rolling 6 design will be used to estimate the MTDRP2D and to determine the dose limiting toxicities DLTs of the escalating doses Once a candidate MTD or RP2D based on 6 subjects has been determined additional evaluable subjects will be enrolled as part of a Phase 1 expansion cohort in order to better describe the safety and tolerability of the MTDRP2D The data from all subjects treated at the MTDRP2D patients from the dose-findingdose-escalation study plus expansion cohort will also be used to assess the stage I efficacy criteria for cohort 2 as part of the Phase 2 design If these criteria are met cohort 2 sample size will be expanded beyond the interim analysis and the Phase 2 study will be initiated in cohort 1
Mirdametinib will be administered twice daily in cycles of 28 days and may be continued for up to 24 months 26 cycles in the absence of disease progression or unacceptable toxicity Doses will be based on the BSA calculated before each cycle of therapy During the DLT period ie cycle 1 all phase 1 participants including those in the phase 1 expansion cohort will receive mirdametinib in dispersible tablets only Thereafter patients who can swallow capsules may transition to capsules if permitted by their specific dose level
Once the phase 2 is open to enrollment participants from the phase 1 on a dose level that differs from the RP2D may choose to change to the RP2D as long as they have not undergone a dose-reduction for toxicity and if the treating physician and the patientfamily agree it is in the best interest of the patient
In Phase 2 of the study participants will be stratified into 3 disease cohorts
Cohort 1 Patients with Newly Diagnosed Low-Grade Glioma
Cohort 2 Patients with Progressive or Recurrent Low-Grade Glioma without Previous MEKi Exposure
Cohort 3 Patients with Progressive or Recurrent Low-Grade Glioma with Previous MEKi Exposure and
Cohort 3A Previously received 6 or more cycles of MEKi therapy and did not progress on MEKi therapy
Cohort 3B Previously treated with MEKi other than mirdametinib and progressed while on MEKi therapy
Therapy will be administered at RP2D in cycles of 28 days and may be continued for up to 24 months 26 cycles in absence of disease progression or unacceptable toxicity Patients in Cohort 3 with previous exposure to mirdametinib may receive a starting dose lower than the RP2D depending on the dose they tolerated during their previous exposure Phase 2 will utilize both the dispersible tablet and capsule formulations
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-2021-05912 | REGISTRY | NCI Clinical Trial Registration Program | None |