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Report for Clinical Trial NCT01089101

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase 1 and Phase II and Re-Treatment Study of AZD6244 for Recurrent or Refractory Pediatric Low Grade Glioma

This phase I/II trial studies the side effects and the best dose of selumetinib and how well it works in treating or re-treating young patients with low grade glioma that has come back (recurrent) or does not respond to treatment (refractory). Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

NCT01089101 Low Grade Glioma Recurrent Childhood Pilocytic Astrocytoma Recurrent Neurofibromatosis Type 1 Recurrent Visual Pathway Glioma Refractory Neurofibromatosis Type 1 Refractory Visual Pathway Glioma
MeSH: Glioma Astrocytoma Neurofibromatoses Neurofibromatosis 1 Neurofibroma Optic Nerve Glioma
HPO: Astrocytoma Glioma Neurofibromas Optic nerve glioma Subependymal giant-cell astrocytoma

3 Interventions

Name: Laboratory Biomarker Analysis

Description: Correlative studies

Type: Other

Treatment (selumetinib)

Name: Pharmacological Study

Description: Correlative studies

Type: Other

Treatment (selumetinib)

Name: Selumetinib

Description: Given PO

Type: Drug

Treatment (selumetinib)


Primary Outcomes

Description: Toxicities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

Measure: Maximum tolerated dose and recommended phase 2 dose of selumetinib determined by dose-limiting toxicities (phase I)

Time: 28 days

Description: 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.

Measure: Stratum-specific objective response (complete response + partial response) rate sustained for 8 weeks (phase II)

Time: 40 weeks

Description: Exact confidence interval estimates will be provided.

Measure: Objective response (objective response = complete response + partial response) (re-treatment study)

Time: Up to 48 weeks

Description: Disease stabilization rates will be measured.

Measure: Disease stabilization rates (re-treatment study)

Time: At 1 year

Secondary Outcomes

Description: 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.

Measure: Plasma drug concentrations and pharmacokinetic parameters (Phase I)

Time: Day 1 of cycle 1

Description: 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.

Measure: Stratum-specific progression-free survival distribution (PFS) (phase II)

Time: 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

Description: 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.

Measure: Presence or absence of BRAF V600E mutations or BRAF KIAA1549 fusion (phase II)

Time: Up to 30 days

Description: Kaplan-Meier estimates of progression-free survival distributions for all eligible patients will be provided. Exact confidence interval estimates will be provided.

Measure: Progression-free survival (retreatment study)

Time: 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

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 V600E

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). --- V600E ---

To assess the sustained response rate of AZD6244 administered at 25 mg/m^2/dose twice daily (BID), in a single arm Phase II setting in patients assigned to strata based on neurofibromatosis (NF)-1 status and presence or absence of v-raf murine sarcoma viral oncogene homolog B (BRAF) aberrations, specifically BRAF V600E mutations and/or BRAF KIAA1549 fusion identified by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), respectively. --- V600E ---



HPO Nodes


HPO:
Astrocytoma
Genes 27
TSC2 APC MSH3 BRCA2 MLH1 TSC1 PMS2 APC IDH1 MSH6 POT1 TSC2 CDKN2A NF2 IFNG MSH3 APC TSC1 NF1 APC TP53 MSH2 ERBB2 IDH1 APC IDH2 NF2
Glioma
Genes 50
TSC2 GLI3 BRCA2 TSC1 LRP5 MLH1 PMS2 APC IDH1 MSH6 POT1 TSC2 CDKN2A NF2 MSH3 MSH6 APC NF1 EPCAM TSC1 TGFBR2 SEMA4A IDH1 IDH2 FAN1 APC MSH3 BMPR1A KRAS MLH1 MSH2 C11ORF95 PMS2 MLH3 PIK3CA NBN RELA SETBP1 IFNG RPS20 NF1 PMS1 CHEK2 APC TP53 MSH2 NBN ERBB2 APC NF2
Neurofibromas
Genes 14
NF2 NF1 PDGFB SDHC SPRED1 NF2 SDHB NF1 NF1 SMARCB1 NF1 SUFU KIT NF2
Optic nerve glioma
Genes 5
NF1 TSC2 TSC1 NF1 IFNG
Subependymal giant-cell astrocytoma
Genes 2
TSC1 TSC2