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An Open-Label, Dose-Escalation, Phase IB II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor GSK1120212 in Combination With Oral Everolimus in Subjects With Solid Tumors

Phase 1
18 Years
Not Enrolling

Thank you

Trial Information

An Open-Label, Dose-Escalation, Phase IB II Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the MEK Inhibitor GSK1120212 in Combination With Oral Everolimus in Subjects With Solid Tumors

MEK112110 is a dose-escalation, open-label study to determine the recommended dose and
regimen for the orally administered MEK inhibitor GSK1120212 dosed in combination with
everolimus in subjects with solid tumors. This will be accomplished using a dose-escalation
procedure starting at low doses of GSK1120212 and everolimus. Dose escalation will continue
based on predefined parameters until the maximum tolerated dose is identified. The
recommended doses and regimens will be selected based on the safety and pharmacokinetic
profiles. The clinical activity of GSK1120212 dosed in combination with everolimus will be
explored further in an expansion cohort consisting of 20 subjects with metastatic pancreatic
cancer. In addition a substudy will be conducted in 40 subjects with KRAS-mutant non-small
cell lung cancer.

Inclusion Criteria:

- Capable of giving written informed consent, which includes compliance with the
requirements and restrictions listed in the consent form.

- Age 18 years old or older and able to swallow oral medication.

- Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology
(ECOG) scale for Dose Escalation Cohort. Subjects with ECOG of 2 can be enrolled for
expansion cohort.

- Tumor Type criteria as listed in the protocol

- Fasting glucose < 126mg/dL

- Male subjects must agree to use one of the contraception methods listed in the

- A female subject is eligible to participate if she is of non-childbearing potential,
and if she is of childbearing potential she must use protocol defined contraception

- Calcium phosphate product less than or equal to 4.0 mmol2/L2 (50 mg2/dL2)

- Adequate organ system function as defined below in the protocol.

Exclusion Criteria:

- Malignancies related to HIV or solid organ transplant.

- Primary malignant brain tumors.

- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior
nitrosoureas or mitomycin C) prior to the first dose of GSK1120212. Chemotherapy
regimens given continuously or on a weekly basis with limited potential for delayed
toxicity are permitted with approval of a GSK Medical Monitor if dosing of that agent
is terminated at least 14 days prior to the first dose of GSK1120212.

- Use of an investigational anti-cancer drug within 28 days or 5 half-lives, whichever
is shorter preceding the first dose of GSK1120212 - as long as a minimum of 14 days
has passed between the last dose of the prior investigational anti-cancer drug and
the first dose of GSK1120212.

- Previous treatment with an mTOR inhibitor unless approved by GSK Medical Monitor.

- Previous treatment with GSK1120212.

- History of sensitivity to any of the study medications, or components thereof or a
history of drug or other allergy that, in the opinion of the investigator or GSK
Medical Monitor, contraindicates their participation.

- Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
chemically related to the study drug, DMSO, or excipients. (To date there are no
known FDA approved drugs chemically related to GSK1120212).

- Use of a prohibited medication (as defined in the protocol).

- Current use of anticoagulants (e.g. warfarin, heparin) at therapeutic levels within
seven days prior to the first dose of GSK1120212. Low dose (prophylactic) low
molecular weight heparin (LMWH) is permitted provided that subject's PT and PTT meet
entry criteria. Subjects required therapeutic levels of LMWH must receive approval
from GSK Medical Monitor and monitored appropriately as clinically indicated.

- Gastrointestinal disease predicted to interfere with absorption of an oral drug,
systemic disease, major surgery, or social/psychological issues that in the opinion
of investigators would jeopardize compliance with protocol.

- History of retinal vein occlusion (RVO) or central serous retinopathy (CSR).

- Predisposing factors to RVO including uncontrolled hypertension, uncontrolled
diabetes, uncontrolled hyperlipidemia, and coagulopathy.

- Visible retinal pathology as assessed by ophthalmologic exam that is considered a
risk factor for RVO or CSR.

- Intraocular pressure > 21mm Hg as measured by tonography.

- Glaucoma diagnosed within 1 month prior to study Day 1.

- Symptomatic or untreated leptomeningeal or brain metastases or spinal cord
compression. Subjects previously treated for these conditions that are asymptomatic
and off corticosteroids for at least two weeks are permitted. Subjects are not
permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs).

- Unresolved toxicity greater than common terminology criteria for adverse events
(CTCAE) grade 1 from previous anti-cancer therapy except alopecia (if applicable)
unless agreed to by a GSK Medical Monitor and the Investigator.

- History of acute coronary syndromes (including unstable angina), coronary
angioplasty, or stenting within the past 24 weeks.

- QTc interval ≥ 480 msecs.

- Class II, III, or IV heart failure as defined by the New York Heart Association
(NYHA) functional classification system.

- Pregnant or lactating female.

- History or active hepatitis B or C.

- History of HIV infection.

- Subjects on chronic antifungal therapy.

- Unwillingness or inability to follow the procedures outlined in the protocol.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

AEs and changes in laboratory values and vital signs

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

GSK Clinical Trials

Investigator Role:

Study Director

Investigator Affiliation:



United States: Food and Drug Administration

Study ID:




Start Date:

August 2009

Completion Date:

November 2011

Related Keywords:

  • Cancer
  • GSK1120212, everolimus, solid tumors, pancreatic cancer, non-small lung cancer, KRAS-mutant
  • cancer



GSK Investigational Site Fort Worth, Texas  76104
GSK Investigational Site Germantown, Tennessee  38138