SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT03711422

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Dose Finding Study of Continuous and Intermittent High-dose (HDI) Afatinib (EGFR TKI) on CNS Metastases and Leptomeningeal Disease (LMD) in Patients With Advanced Refractory EGFR Mutation Positive Non-small Cell Lung Cancer

Brain metastases occurs in up to 50% of patients with EGFR mutant NSCLC. Leptomeningeal disease is a subset of patients with brain metastases for which there remains an unmet need. This trial aims to evaluate the role of two dosing schedules of afatinib in management of leptomeningeal disease in EGFR mutant NSCLC, specifically to determine Central Nervous System (CNS) penetration of afatinib, as well as clinical activity. Patients will start on daily dosing initially followed by pulsed intermittent dosing should we observe no clinical activity. A secondary objective is to identify the resistance spectrum in leptomeningeal disease. It is anticipated that optimal dosing schedule of afatinib e.g. pulsed dosing may improve CNS disease control.

NCT03711422 Non-small Cell Lung Cancer Leptomeningeal Disease Central Nervous System Metastases
MeSH:Lung Neoplasms Carcinoma, Non-Small-Cell Lung Neoplasm Metastasis Meningeal Neoplasms
HPO:Neoplasm of the lung Non-small cell lung carcinoma

2 Interventions

Name: Afatinib

Description: 40mg daily
Type: Drug
Group Labels: 1

Part A

Name: Afatinib

Description: 160mg for 3 days every 3 weeks
Type: Drug
Group Labels: 1

Part B


Primary Outcomes

Description: To assess the difference in drug ratio from two difference dosing of afatinib

Measure: Afatinib concentration in plasma using standard dosing and high intermittent dosing

Time: Day 1 to Day 29 of drug treatment

Description: To assess the difference in drug ratio from two difference dosing of afatinib

Measure: Afatinib concentration in Cerebral Spinal Fluid (CSF) using standard dosing and high intermittent dosing

Time: Part A: Day 15; Part B: Day 17 and 31

Measure: Neurological Progression Free Survival

Time: From time of first study drug administration until first occurrence of disease progression, or death from any cause, up to 2 years

Measure: Neurological Response Rate

Time: From time of first study drug administration until first occurrence of disease progression, up to 2 years

Measure: Overall Survival

Time: From time of first study drug administration to death from any cause, up to 2 years

Secondary Outcomes

Description: To detect EGFR T790M and activating mutation status

Measure: Cell-free DNA sequencing of Cerebrospinal Fluid

Time: From time of first study drug administration to end of study treatment, up to 2 years

Description: To assess the physical, physiological and social functions. The scale ranges from 1="not all all" to 4-"very much"

Measure: European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30

Time: From time of first study drug administration through to end of study treatment or disease progression, up to 2 years

Description: To assess future uncertainty, visual disorder, motor dysfunction, and communication deficit. The scale ranges from 1="not all all" to 4-"very much"

Measure: EORTC Quality of Life Questionnaire Brain Cancer Module

Time: From time of first study drug administration through to end of study treatment or disease progression, up to 2 years

Description: AEs will be graded according to CTCAE, Version 4.0

Measure: Incidences of treatment-emergent adverse events (AE)

Time: From time of first study drug administration to 28 days after last treatment administration

Purpose: Treatment

Allocation: Non-Randomized

Parallel Assignment


There is one SNP

SNPs


1 T790M

To detect EGFR T790M and activating mutation status. --- T790M ---



HPO Nodes


HPO: