SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03516214

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

An Open-label, Multicenter, Phase I Dose-escalation Trial of EGF816 and Trametinib in Patients With Non-small Cell Lung Cancer and Acquired EGFR p.T790M-positive Resistance to 1st or 2nd Generation EGFR TKI Therapy

The aim of this trial is to identify the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) for a continuous treatment with EGF816 and trametinib in patients with epithelial growth factor receptor (EGFR) p.T790M-positive resistance to EGFR inhibition.

NCT03516214 Bronchial Neoplasms
MeSH: Carcinoma, Non-Small-Cell Lung Bronchial Neoplasms
HPO: Bronchial neoplasm Non-small cell lung carcinoma

2 Interventions

Name: EGF816

Description: Continuous oral treatment (once daily) with the 3rd generation EGFR inhibitor EGF816.

Type: Drug

EGF816 and trametinib

Name: Trametinib

Description: Continuous oral treatment (once daily) with the MEK inhibitor trametinib.

Type: Drug

EGF816 and trametinib


Primary Outcomes

Description: Incidence of dose-limiting-toxicities (DLT) that occur during the DLT period (i.e. first 4 weeks of treatment) of each patient in the dose-escalation part (N=18)

Measure: Incidence of dose-limiting-toxicities (DLT) of the combination of EGF816 and trametinib to assess the maximum tolerated dose (MTD)/recommended phase II dose (RP2D)

Time: Approximately one and a half years (from FPFV until the end of the DLT period of the last patient included into the trial or until death of the last patient, whichever occurs first)

Secondary Outcomes

Measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.03

Time: Approximately four years (from FPFV until the completion of the clinical trial)

Measure: Number of patients who experienced dose interruptions or reductions

Time: Approximately four years (from FPFV until the end-of-treatment visit of the last patient or until death of the last patient, whichever occurs first)

Measure: Objective response rate (ORR) according to RECIST 1.1

Time: Approximately 4 years (from FPFV until the progression of the last patient treated within the trial or until death of the last patient, whichever occurs first)

Measure: Disease control rate (DCR) according to RECIST 1.1

Time: Approximately 4 years (from FPFV until the progression of the last patient treated within the trial or until death of the last patient, whichever occurs first)

Measure: Progression-free survival (PFS) according to RECIST 1.1

Time: Approximately 4 years (from FPFV until the progression of the last patient treated within the trial or until death of the last patient, whichever occurs first)

Measure: Duration of response (DOR) according to RECIST 1.1

Time: Approximately 4 years (from FPFV until the progression of the last patient treated within the trial or until death of the last patient, whichever occurs first)

Measure: Time to response (TTR) according to RECIST 1.1

Time: Approximately 4 years (from FPFV until the progression of the last patient treated within the trial or until death of the last patient, whichever occurs first)

Measure: overall survival (OS)

Time: Approximately 4 years (from FPFV until the progression of the last patient treated within the trial or until death of the last patient, whichever occurs first)

Measure: Plasma concentration vs time profiles - plasma PK parameters of EGF816 and trametinib

Time: Approximately two years (from FPFV until the completion of four months of treatment of the last patient or until death of the last patient, whichever occurs first)

Other Outcomes

Measure: Massively parallel sequencing (MPS), FISH and phospho-immunoblots of pre-treatment tumour samples in order to assess potential predictive markers for response and resistance

Time: Approximately one and a half years (from FPFV until the inclusion of the last patient)

Measure: Massively parallel sequencing (MPS), FISH and phospho-immunoblots of post-treatment tumour samples in order to assess potential predictive markers for response and resistance

Time: Approximately four years (from the first progressing patient until the last progressing patient or death of the last patient, whichever occurs first)

Measure: MPS of cell-free DNA (cfDNA) at baseline, during treatment and at progression to assess the value of cell-free plasma DNA (cfDNA) for assessment of predictive molecular markers of response and resistance and for monitoring patients under therapy

Time: Approximately four years (from FPFV until the progression of the last patient or death of the last patient, whichever occurs first)

Measure: Establishment of conditionally reprogrammed tumour cells (CRCs) from fresh tumour tissue for the study of resistance mechanisms and drug sensitivity

Time: Approximately four years (from the first progressing patient until the last progressing patient or death of the last patient, whichever occurs first)

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 T790M

EGF816 and Trametinib in Patients With Non-small Cell Lung Cancer and T790M-positive Resistance to EGFR TKI Therapy The aim of this trial is to identify the maximum tolerated dose (MTD)/recommended phase II dose (RP2D) for a continuous treatment with EGF816 and trametinib in patients with epithelial growth factor receptor (EGFR) p.T790M-positive resistance to EGFR inhibition. --- T790M ---



HPO Nodes


HPO:
Bronchial neoplasm
Non-small cell lung carcinoma
Genes 2
TP53 BAP1