Selumetinib in Treating Young Patients With Recurrent or Refractory Low Grade Glioma
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|ClinicalTrials.gov Identifier: NCT01089101|
Recruitment Status : Recruiting
First Posted : March 18, 2010
Last Update Posted : May 15, 2020
|Condition or disease||Intervention/treatment||Phase|
|Low Grade Glioma Recurrent Childhood Pilocytic Astrocytoma Recurrent Neurofibromatosis Type 1 Recurrent Visual Pathway Glioma Refractory Neurofibromatosis Type 1 Refractory Visual Pathway Glioma||Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Selumetinib||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||180 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 and Phase II and Re-Treatment Study of AZD6244 for Recurrent or Refractory Pediatric Low Grade Glioma|
|Actual Study Start Date :||April 19, 2010|
|Estimated Primary Completion Date :||December 31, 2022|
Experimental: Treatment (selumetinib)
Patients receive selumetinib PO BID on days 1-28. Cycles repeat every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience a sustained objective response from selumetinib on the phase I or phase II portions of the trial, and who have completed 2 years of treatment and stopped study drug may be enrolled on the re-treatment study after progression/recurrence. Patients in the re-treatment study may continue treatment indefinitely in the absence of disease progression or unacceptable toxicities.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- Maximum tolerated dose and recommended phase 2 dose of selumetinib determined by dose-limiting toxicities (phase I) [ Time Frame: 28 days ]Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Stratum-specific objective response (complete response + partial response) rate sustained for 8 weeks (phase II) [ Time Frame: 40 weeks ]For each stratum separately exact confidence interval estimates will be provided for the true, unknown rates of objective response. In addition, the confirmed sustained objective response rate observed during treatment by cumulative incidence functions will be estimated. This provides not only an overall estimate of the response rate but also an estimate of the timing of responses as a function of number of months of treatment.
- Objective response (objective response = complete response + partial response) (re-treatment study) [ Time Frame: Up to 48 weeks ]Exact confidence interval estimates will be provided.
- Disease stabilization rates (re-treatment study) [ Time Frame: At 1 year ]Disease stabilization rates will be measured.
- Plasma drug concentrations and pharmacokinetic parameters (Phase I) [ Time Frame: Day 1 of cycle 1 ]Plasma drug concentrations and pharmacokinetic parameters volume of the central compartment, elimination rate constant, half-life, apparent oral clearance, and area under the plasma concentration time curve.
- Stratum-specific progression-free survival distribution (PFS) (phase II) [ Time Frame: From the date of initial treatment to the earliest date of disease progression, second malignancy or death for subjects who fail; and to the date of last contact for subjects who remain at risk for failure assessed for up to 30 days ]Kaplan-Meier estimates of distributions of PFS all eligible subjects who received at least one dose of selumetinib will be provided separately for each stratum. It is unlikely that sufficient numbers of subjects will be followed until death to statistically support estimation of the survival distributions but survival estimation will also be considered.
- Presence or absence of BRAF V600E mutations or BRAF KIAA1549 fusion (phase II) [ Time Frame: Up to 30 days ]Will be assessed by immunohistochemistry and fluorescence in situ hybridization, respectively. Frequency tables summarizing the presence and absence of BRAF aberrations in all patients from whom tissue is available will be provided. The association of presence/absence and type of BRAF aberrations versus PFS will be explored via Kaplan-Meier-plots. Log-rank tests and/or Cox regression models may also be used to assess statistical associations between BRAF and PFS provided more than 10 events are observed in a given strata to make such assessments meaningful.
- Progression-free survival (retreatment study) [ Time Frame: From the date of re-treatment initiation to the earliest date of disease progression, second malignancy or death for patients who fail; and the last contact for patients who remain at risk for failure, assessed up to 30 days ]Kaplan-Meier estimates of progression-free survival distributions for all eligible patients will be provided. Exact confidence interval estimates will be provided.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01089101
|Principal Investigator:||Jason R Fangusaro||Pediatric Brain Tumor Consortium|