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An Open-label, Randomized, 2-treatment, 2-period, 2-way Crossover, Single-dose Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies

Phase 1
18 Years
Open (Enrolling)

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Trial Information

An Open-label, Randomized, 2-treatment, 2-period, 2-way Crossover, Single-dose Study to Determine the Relative Bioavailability of the MEK Inhibitor, Trametinib, in Subjects With Solid Tumor Malignancies

Inclusion Criteria:

- Has provided signed, written informed consent.

- Male or female, age >=18 years of age at the time of signing the informed consent

- Has histologically or cytologically confirmed diagnosis of a solid tumor malignancy
that is not responsive to standard therapy (ies) or for which there is no approved

- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Able to swallow and retain orally administered medication and does not have any
clinically significant gastrointestinal (GI) abnormalities that may alter absorption
such as malabsorption syndrome or major resection of the stomach or bowels.

- All prior treatment-related toxicities must be National Cancer Institute - Common
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.0 <=Grade 1 (except
alopecia) at the time of enrollment.

- Has adequate baseline organ function as defined: ANC >=1.2×10^9/liter (L),
hemoglobin>=9 gram (g)/deciliter (dL), Platelets>=75×10^9/L, partial thromboplastin
time (PTT), prothrombin time (PT) and International normalization ratio (INR) <=1.5
times upper limit of normal (ULN), albumin >=2.5 g/dL, total bilirubin <=1.5 times
ULN alanine aminotransferase (ALT) <=2.5 times ULN, Creatinine or calculated
creatinine clearance >=50 milliliter (mL)/minute (min) and left ventricular ejection
fraction (LVEF)>=lower limit of normal (LLN) by echocardiogram (ECHO) or multigated
acquisition scan (MUGA).

- Women of childbearing potential must have a negative serum pregnancy test within 14
days of first dose of study treatment and agree to use effective contraception,
during the study and for 4 months following the last dose of study treatment.

Exclusion Criteria:

- Prior exposure to a mitogen-activated extracellular signal-regulated kinase (MEK)

- Anti-cancer therapy (e.g., chemotherapy with delayed toxicity, extensive radiation
therapy, immunotherapy, biologic therapy, or major surgery) within 21 days prior to
randomization; chemotherapy regimens without delayed toxicity within 14 days prior to

- Female Subjects: Lactating or actively breastfeeding.

- Has participated in a clinical trial and received investigational drug within 30
days, 5 half-lives or twice the duration of the biological effect of the
investigational product (IP), whichever is longer, prior to randomization in this

- Has participated in a study that resulted in or made a donation of blood or blood
products in excess of 500 mL within 56 days of the first dose of study treatment.

- History or presence of hepatic insufficiency (excluding metastatic hepatic

- History of interstitial lung disease or pneumonitis.

- Known Human Immunodeficiency Virus, Hepatitis B Virus (HBV), or Hepatitis C Virus
(HCV) infection

- Subjects with laboratory evidence of cleared HBV and HCV infection will be permitted.

- Has a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to study treatment, or excipients, or to DMSO.

- Currently using a prohibited medication or requires the use of any of the prohibited
medications during the study. Use of anticoagulants such as warfarin is permitted
provided INR must be monitored in accordance with local institutional practice.

- Has a history of another malignancy. Subjects who have been disease-free for 3 years
or subjects with a history of a completely resected non-melanoma skin cancer and/or
subjects with indolent second malignancies are eligible.

- Any serious and/or unstable pre-existing medical disorder (aside from malignancy
exception above), psychiatric disorder, or other conditions that could interfere with
subject's safety, obtaining informed consent or compliance to the study procedures.

- Has a history or current evidence/risk of retinal vein occlusion (RVO) or central
serous retinopathy (CSR).

- Symptomatic or untreated leptomeningeal or brain metastases, or spinal cord

- Left ventricular ejection fraction (LVEF), as measured by ECHO or MUGA scan, below
the institutional LLN, or if a LLN does not exist at an institution, <50%.

- QT interval corrected for heart rate using the Bazett formula (QTcB) >=480
millisecond (msec).

- History or current evidence of cardiovascular risk including any of the following:
current clinically significant uncontrolled arrhythmias, acute coronary syndromes
(including myocardial infarction and unstable angina), coronary angioplasty, or
stenting within 6 months prior to randomization, current >= Class II congestive heart
failure as defined by New York Heart Association (NYHA), treatment-refractory
hypertension defined as a blood pressure of systolic blood pressure (SBP) >140
millimeters of mercury (mmHg) and/or diastolic blood pressure (DBP) >90 mmHg which
cannot be controlled by anti-hypertensive therapy, has an intra-cardiac defibrillator
or permanent pacemaker and known cardiac metastases.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label

Outcome Measure:

Corrected Cmax of GSK1120212B

Outcome Description:

Pharmacokinetic data will include corrected maximum plasma concentration (Cmax) of GSK1120212B. Comparison of Cmax will enable to determine the relative bioavailability of the test formulation with lower DMSO content (Treatment B) and the standard reference formulation (Treatment A). Period 2 PK parameters will be corrected for residual concentrations from Period 1 (based on individual estimates of t1/2) to remove the carry-over effect.

Outcome Time Frame:

Period 1 and 2: Day 1 pre-dose within 15 minutes (mins) of planned study treatment administration (serves as the 168-hour [hr] sample for Period 1), 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 10 hrs post-dose; Days 2 to 7: post dose at 24 hrs (Day 2), 48 hrs (

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

February 2013

Completion Date:

June 2014

Related Keywords:

  • Cancer
  • GSK1120212
  • DMSO content
  • pharmacokinetics
  • solid tumors
  • MEK inhibitor
  • dissolution
  • trametinib
  • relative bioavailability



GSK Investigational SitePhoenix, Arizona  85013 - 4496