A Phase IB Combination Study of MEK Inhibitor GSK1120212 With Gemcitabine in Subjects With Solid Tumors
- 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
- Histologically or cytologically confirmed diagnosis of a solid tumor malignancy that
is either relapsed or refractory, or potentially responsive to gemcitabine.
- Tumor Type criteria as listed in protocol.
- Male subjects must agree to use one of the contraception methods listed in protocol.
- A female subject is eligible to participate if she is of non-childbearing potential
as defined in the protocol or postmenopausal as defined in the protocol. If of
child-bearing potential, she agrees to use protocol specified contraceptive methods
- Adequate organ system function as defined below in the protocol.
- Chemotherapy, radiotherapy, or immunotherapy within 28 days (or 42 days for prior
nitrosoureas or mitomycin C) prior to the first dose of GSK1120212.
- Use of an investigational anti-cancer drug within 28 days or five 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.
- 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, dimethy sulfoxide (DMSO), or excipients (See
- Use of a prohibited medication (as defined in protocol) or current use of
anticoagulants (e.g. warfarin, heparin, low molecular weight heparin) at therapeutic
levels. Low dose (prophylactic) anticoagulants are permitted provided that subject's
prothrombin time (PT) and partial thromboplastin time (PTT) meet entry criteria.
- Gastrointestinal disease predicted to interfere with absorption of an oral drug.
- History of retinal vein occlusion (RVO) or central serous retinopathy.
- Visible retinal pathology as assessed by ophthalmologic exam that is considered a
risk factor for retinal vein thrombosis.
- Glaucoma diagnosed within one month prior to study day 1.
- Intraocular pressure > 21mm Hg as measured by tonography.
- 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 months 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 v4.0) grade 1 from previous anti-cancer therapy.
- History of acute coronary within the past 24 weeks.
- QTc interval greater than or equal to 480 mili seconds (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 of hepatitis B or C. NOTE: Subjects with evidence of cleared hepatitis B
infection are permitted [Hepatitis B Surface Antigen (HBsAg) negative, anti-HBsAg
positive and anti Hepatitis B core antigen (HBc) positive.]