Ignite Creation Date:
2024-05-06 @ 11:07 AM
Last Modification Date:
2024-10-26 @ 12:40 PM
Study NCT ID:
NCT03434262
Status:
COMPLETED
Last Update Posted:
2024-05-31
First Post:
2018-02-09
Brief Title:
SJDAWN St Jude Childrens Research Hospital Phase 1 Study Evaluating Molecularly-Driven Doublet Therapies for Children and Young Adults With Recurrent Brain Tumors
Sponsor:
St Jude Childrens Research Hospital
Organization:
St Jude Childrens Research Hospital
Study Overview
Official Title:
Molecularly-Driven Doublet Therapy for All Children With Refractory or Recurrent CNS Malignant Neoplasms and Young Adults With Refractory or Recurrent SHH Medulloblastoma
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Approximately 90 of children with malignant brain tumors that have recurred or relapsed after receiving conventional therapy will die of disease Despite this terrible and frustrating outcome continued treatment of this population remains fundamental to improving cure rates Studying this relapsed population will help unearth clues to why conventional therapy fails and how cancers continue to resist modern advances Moreover improvements in the treatment of this relapsed population will lead to improvements in upfront therapy and reduce the chance of relapse for all Novel therapy and more importantly novel approaches are sorely needed This trial proposes a new approach that evaluates rational combination therapies of novel agents based on tumor type and molecular characteristics of these diseases The investigators hypothesize that the use of two predictably active drugs a doublet will increase the chance of clinical efficacy The purpose of this trial is to perform a limited dose escalation study of multiple doublets to evaluate the safety and tolerability of these combinations followed by a small expansion cohort to detect preliminary efficacy In addition a more extensive and robust molecular analysis of all the participant samples will be performed as part of the trial such that we can refine the molecular classification and better inform on potential response to therapy In this manner the tolerability of combinations can be evaluated on a small but relevant population and the chance of detecting antitumor activity is potentially increased Furthermore the goal of the complementary molecular characterization will be to eventually match the therapy with better predictive biomarkers
PRIMARY OBJECTIVES
To determine the safety and tolerability and estimate the maximum tolerated doserecommended phase 2 dose MTDRP2D of combination treatment by stratum
To characterize the pharmacokinetics of combination treatment by stratum
SECONDARY OBJECTIVE
To estimate the rate and duration of objective response and progression free survival PFS by stratum
PRIMARY OBJECTIVES
To determine the safety and tolerability and estimate the maximum tolerated doserecommended phase 2 dose MTDRP2D of combination treatment by stratum
To characterize the pharmacokinetics of combination treatment by stratum
SECONDARY OBJECTIVE
To estimate the rate and duration of objective response and progression free survival PFS by stratum
Detailed Description:
Patients will be stratified by the molecular and histologic characteristics of their tumor to one of three treatment strata
STRATUM A
Combination Treatment ribociclib and gemcitabine
Patient Population Participants with a diagnosis of refractory or recurrent medulloblastoma Group 34 or refractory or recurrent ependymoma including ependymoma not otherwise specified NOS WHO Grade III ependymoma RELA fusion positive anaplastic ependymoma ependymoma NOS WHO grade II
STRATUM B
Combination Treatment ribociclib and trametinib
Patient Population Participants with a diagnosis of one of the following refractory or recurrent CNS diseases medulloblastoma sonic hedgehog SHH medulloblastoma WNT high grade glioma including high grade glioma NOS WHO Grade III or IV anaplastic astrocytoma IDH mutant glioblastoma IDH-wildtype glioblastoma IDH-mutant diffuse midline glioma H3K27-mutant anaplastic oligodendroglioma IDH mutant and 1p19q-codeleted anaplastic pleomorphic xanthoastrocytoma or select central nervous system CNS embryonal tumors including embryonal tumors with multilayered rosettes C19MC-altered embryonal tumors with multilayered rosettes not otherwise specified NOS medulloepithelioma CNS neuroblastoma CNS ganglioneuroblastoma CNS embryonal tumor NOS atypical teratoidrhabdoid tumor CNS embryonal tumor with rhabdoid features
STRATUM C
Combination Treatment ribociclib and sonidegib
Patient Populations Participants with refractory or recurrent medulloblastoma SHH 6 months off smoothened inhibitor presence of 9q loss or PTCH1 mutant skeletally mature
The rolling 6 design will be used separately in each stratum to estimate the MTD or RP2D and determine the dose-limiting toxicity DLT of the combination of escalating doses Therapy will be administered 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 Stratum A participants may continue therapy past 24 months in absence of disease progression or unacceptable toxicity
Patients will receive doublet therapy in cycles of 28 days The dose-limiting toxicity DLT-evaluation period will consist of the first cycle ie first 4 weeks of therapy Research participants will be evaluated at least once a week during the DLT-evaluation period and at regular intervals thereafter Standard eg physical exam blood tests and disease evaluations tests will be obtained at regular intervals Research-associated evaluations eg pharmacokinetic studies etc will also be obtained during therapy Treatment may be continued for up to 2 years in the absence of disease progression or unacceptable toxicity Stratum A participants may continue past 2 years in the absence of disease progression or unacceptable toxicity
STRATUM A
Combination Treatment ribociclib and gemcitabine
Patient Population Participants with a diagnosis of refractory or recurrent medulloblastoma Group 34 or refractory or recurrent ependymoma including ependymoma not otherwise specified NOS WHO Grade III ependymoma RELA fusion positive anaplastic ependymoma ependymoma NOS WHO grade II
STRATUM B
Combination Treatment ribociclib and trametinib
Patient Population Participants with a diagnosis of one of the following refractory or recurrent CNS diseases medulloblastoma sonic hedgehog SHH medulloblastoma WNT high grade glioma including high grade glioma NOS WHO Grade III or IV anaplastic astrocytoma IDH mutant glioblastoma IDH-wildtype glioblastoma IDH-mutant diffuse midline glioma H3K27-mutant anaplastic oligodendroglioma IDH mutant and 1p19q-codeleted anaplastic pleomorphic xanthoastrocytoma or select central nervous system CNS embryonal tumors including embryonal tumors with multilayered rosettes C19MC-altered embryonal tumors with multilayered rosettes not otherwise specified NOS medulloepithelioma CNS neuroblastoma CNS ganglioneuroblastoma CNS embryonal tumor NOS atypical teratoidrhabdoid tumor CNS embryonal tumor with rhabdoid features
STRATUM C
Combination Treatment ribociclib and sonidegib
Patient Populations Participants with refractory or recurrent medulloblastoma SHH 6 months off smoothened inhibitor presence of 9q loss or PTCH1 mutant skeletally mature
The rolling 6 design will be used separately in each stratum to estimate the MTD or RP2D and determine the dose-limiting toxicity DLT of the combination of escalating doses Therapy will be administered 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 Stratum A participants may continue therapy past 24 months in absence of disease progression or unacceptable toxicity
Patients will receive doublet therapy in cycles of 28 days The dose-limiting toxicity DLT-evaluation period will consist of the first cycle ie first 4 weeks of therapy Research participants will be evaluated at least once a week during the DLT-evaluation period and at regular intervals thereafter Standard eg physical exam blood tests and disease evaluations tests will be obtained at regular intervals Research-associated evaluations eg pharmacokinetic studies etc will also be obtained during therapy Treatment may be continued for up to 2 years in the absence of disease progression or unacceptable toxicity Stratum A participants may continue past 2 years in the absence of disease progression or unacceptable toxicity
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-2018-00284 | REGISTRY | NCI Clinical Trial Registration Program | None |