NCT01138085

Safety, Pharmacokinetics (PK) of AKT and MEK Combination

Completed Phase 1 Last updated 13 November 2017

What this trial tests

Phase 1 trial testing GSK1120212 in Cancer in 240 participants. Completed in 19 November 2014.

Timeline

4 May 2010

Primary endpoint
19 November 2014

19 November 2014

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	240
Start date	4 May 2010
Primary completion	19 November 2014
Estimated completion	19 November 2014
Sites	10 locations across United States

Drugs / interventions tested

• GSK1120212 — full drug profile →
• GSK2141795 — full drug profile →

Conditions studied

• Cancer — all drugs for Cancer →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study is a Phase 1 dose-escalation open-label study to determine the recommended Phase II dose (RP2D) and regimen for the combination of the orally administered MEK inhibitor GSK1120212 and the orally administered AKT kinase inhibitor GSK2141795. The study consists of two parts. Part 1A will identify the maximum tolerated dose (MTD) using a Zone-Based, modified 3 plus 3 dose escalation procedure. The starting dose (Zone 1, Cohort 1) will be 0.5mg GSK1120212 combined with 25mg GSK2141795. Dose escalation will continue based on predefined parameters until a MTD is established. The initial regimen for dose escalation in Part 1A will be continuous oral daily dosing. Once the continuous daily dosing MTD or RP2D has been established in Part 1A, Part 1B will explore alternate dosing schedule(s) in which the dosing schedule may be adjusted for either GSK1120212 or GSK2141795. Dose escalation will proceed using a 3 plus 3 dose escalation procedure until an MTD or RP2D of that alternate schedule is defined. Part 2 will explore further in specific tumor types the safety, tolerability, clinical activity, pharmacokinetic (PK) and pharmacodynamic (PD) properties of the combination of GSK1120212 and GSK2141795 at the recommended dose(s) and regimen(s) identified in Part 1.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. A central role for RAF→MEK→ERK signaling in the genesis of pancreatic ductal adenocarcinoma.
   Collisson EA, Trejo CL, Silva JM, Gu S, et al · · 2012 · cited 252× · PMID 22628411 · DOI 10.1158/2159-8290.cd-11-0347
2. Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascade inhibitors: how mutations can result in therapy resistance and how to overcome resistance.
   McCubrey JA, Steelman LS, Chappell WH, Abrams SL, et al · · 2012 · cited 242× · PMID 23085539 · DOI 10.18632/oncotarget.659
3. Recent advances in targeted strategies for triple-negative breast cancer.
   Zhu S, Wu Y, Song B, Yi M, et al · · 2023 · cited 200× · PMID 37641116 · DOI 10.1186/s13045-023-01497-3
4. Maximising the potential of AKT inhibitors as anti-cancer treatments.
   Brown JS, Banerji U. · · 2017 · cited 184× · PMID 27919797 · DOI 10.1016/j.pharmthera.2016.12.001
5. Racial Disparity and Triple-Negative Breast Cancer in African-American Women: A Multifaceted Affair between Obesity, Biology, and Socioeconomic Determinants.
   Siddharth S, Sharma D. · · 2018 · cited 170× · PMID 30558195 · DOI 10.3390/cancers10120514
6. NRAS mutant melanoma: biological behavior and future strategies for therapeutic management.
   Fedorenko IV, Gibney GT, Smalley KS, Smalley KS. · · 2013 · cited 123× · PMID 23069660 · DOI 10.1038/onc.2012.453
7. Targeting the RAS oncogene.
   Takashima A, Faller DV. · · 2013 · cited 95× · PMID 23360111 · DOI 10.1517/14728222.2013.764990
8. Combating pancreatic cancer with PI3K pathway inhibitors in the era of personalised medicine.
   Conway JR, Herrmann D, Evans TJ, Morton JP, et al · · 2019 · cited 75× · PMID 30396902 · DOI 10.1136/gutjnl-2018-316822