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Report for Clinical Trial NCT00880321

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I, Open-Label, Multiple-Dose, Dose-Escalation Study to Investigate the Safety, Pharmacokinetics, and Pharmacodynamics of the BRAF Inhibitor GSK2118436 in Subjects With Solid Tumors

BRF112680 is a first-time-in-human study to establish the recommended dose and schedule of the orally administered GSK2118436. The recommended dose and regimen will be selected based on the safety, pharmacokinetic, and pharmacodynamic profiles observed after the treatment of subjects with solid tumors. This is a two-part study. Part 1 will identify the recommended Part 2 dose using a dose-escalation procedure. Escalation may proceed until either a maximum tolerated dose is established, or the toxicokinetic safety limit is reached. The recommended Part 2 dose will be expanded to up to 12 patients. Part 2 will explore further the safety, tolerability, and clinical activity of GSK2118436 in subjects with BRAF mutation-positive tumors. In addition, the effect of GSK2118436 on midazolam will be assessed in a subset of patients in Part 2. Biologically active doses will be identified by measurement of pharmacodynamic markers in tumor tissue and blood across a range of doses and these doses may be explored in Part 2.

NCT00880321 Cancer

3 Interventions

Name: GSK2118436

Description: Dose escalation with GSK2118436 may proceed until either a maximum tolerated dose is established, or the toxicokinetic safety limit is reached.

Type: Drug

Part 1

Name: GSK2118436

Description: Part 2 will use the recommended Part 2 dose of GSK2118436 identified during Part 1 of the study. Biologically active doses will be identified by measurement of pharmacodynamic markers in tumor tissue and blood across a range of doses and these doses may be explored in Part 2.

Type: Drug

Part 2

Name: Midazolam

Description: Midazolam will be administered alone and with GSK2118436 in a sub-set of subjects in Part 2 to study the effect of GSK2118436 on CYP3A using midazolam as a probe.

Type: Drug

Part 2


Primary Outcomes

Measure: PK data, AEs, changes in laboratory values and vital signs, physical exam, clinical testing and PD data

Time: 21 days

Secondary Outcomes

Measure: GSK2118436 and its metabolite, PK parameters per protocol following single- and repeat-dose administration of GSK2118436

Time: 15 days

Measure: Change in PD markers including IL-8 in blood, pERK and other markers in tumor biopsies.

Time: 15 days

Measure: Correlation between PK, PD, and clinical endpoints.

Time: 15 days

Measure: Tumor response as defined by Response Evaluation Criteria in Solid Tumors (RECIST v1.0)

Time: approximately once every 2 months until the end of participation

Measure: Urinary ratio of 6-beta-hydroxycortisol to cortisol ratio

Time: 15 days

Measure: GSK2118436 PK parameters per protocol with and without food

Time: 15 days

Measure: Metabolic profiling in plasma and urine

Time: 15 days

Measure: Midazolam PK parameters per protocol

Time: 15 days

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 V600E

- Part 2/Cohort C only: Must have BRAF positive melanoma with the V600E mutation. --- V600E ---



HPO Nodes