GSK1120212+GSK2141795 for Cervical Cancer

Before the research starts (screening): The participant will be asked to undergo some
screening tests or procedures to find out if they can be in the research study. Many of these
tests and procedures are likely to be part of regular cancer care and may be done even if it
turns out that the participant does not take part in the research study. If the participant
has had some of these tests or procedures recently, they may or may not have to be repeated.

- A medical history, which includes questions about the participant's health, current
medications, and any allergies.

- Physical exam, including height and weight

- An eye exam, by an eye specialist

- Performance status, the investigator will ask the participant questions about how they
are able to carry on with your usual activities.

- Vital signs, including blood pressure, pulse, body temperature and respiratory rate

- An assessment of the participant's tumor by CT (Computerized Tomography) scan or MRI
(Magnetic Resonance Imaging), of their chest, stomach area, and pelvis.

- Blood tests (approximately 2-3 tablespoons) including hematology, chemistry, liver
function, kidney function, blood sugar levels, blood clotting levels

- Electrocardiogram (EKG), a test to check the participant's heart's rhythm

- Echocardiogram (ECHO), a test to check the participant's heart's structure and function.

- Serum pregnancy test if the participant are capable of becoming pregnant

If the results of the above tests show that the participant is eligible to participate in the
research study, the participant will begin the study treatment. If the participant does not
meet the eligibility criteria, the participant will not be able to participate in this
research study.

If these tests show that the participant is eligible to participate in the research study,
the participant will begin the study treatment. If the participant does not meet the
eligibility criteria, the participant will not be able to participate in this research study.

Additional research procedures to be performed at the time of screening:

- Archival tumor testing: During this study, additional tests will be performed on a sample
of the participant's original tumor that has been stored in your institution's tissue banks.
These tests will be performed on tumor tissue samples from previous biopsies or surgeries for
the participant's cancer. The research done on these samples will involve looking at DNA and
proteins in the participant's cancer to see if researchers can learn more about the
participant's type of cancer and understand how trametinib and GSK2141795 might work on their
tumor. Testing of this sample will not require the participant to undergo any additional
procedures.

TISSUE COLLECTIONS/OWNERSHIP: Participation in this protocol involves providing specimen(s)
of the participant's tissue. Please know that if the investigator leaves the institution, the
research and the tissue might remain at the DF/HCC or might be transferred to another
institution.

- Additional Blood tests: Approximately 2 tablespoons of blood will be collected for
research testing. This testing will involve looking at DNA and proteins in the
participant's blood to compare them with those seen in their cancer. This will be drawn
before the participant begin taking the study drug. These research sample collections
are a required part of this research study. If the participant does not wish to undergo
these procedures, the participant may not participate in this research study.

- Optional pre and post tumor biopsies: Before the participant begin receiving the study
drug, your doctor will arrange for a procedure where your tumor will be biopsied. Your
entire tumor or part of your tumor might be removed (excisional biopsy) or a small
sample of the tumor might be removed using a needle (needle biopsy, fine needle
aspirate) with guidance under radiographic studies. This will also occur before the
participant begins treatment and between 2-4 weeks after treatment has started.

After the screening procedures confirm that the participant is eligible to participate in the
research study:

Study Drugs:

If the participant decides to take part in this research study, the participant will be given
a study drug diary for each treatment cycle. The participant will be asked to complete a drug
diary to record when they took each dose or to give a reason if the participant did not take
the study drugs. At the end of each cycle, the participant should return the pill bottles and
all of the remaining pills prior to starting the next cycle. The participant will receive a
new set of pills and new diary if the participant is to continue the next cycle.

Clinical Exams: During all cycles the participant will have a physical exam, and will be
asked questions about their general health and specific questions about any problems that
they might having and any medications the participant may be taking.

The participant can expect the following while they are a participant on this study.

At the beginning of each cycle (one cycle equals 28 days):

- Recording of any health problems, including side effects of the study drugs

- List of medications taken since the last visit

- Physical examination (including measurement of vital signs, such as blood pressure,
breathing rate, heart rate, temperature and weight)

- Evaluation of the participant's performance status (the ability to carry on daily
activities)

- Blood samples (approximately 2-3 tablespoons of blood will be taken) to evaluate the
participant's blood counts, electrolytes, liver function, kidney function and blood
sugar levels.

- EKG, a test to check the participant's heart's rhythm. This will be performed at the
start on each cycle.

Once a week during the first cycle:

- The participant will be called by a member of the study team to record any health
problems, including side effects from the study drugs and any changes in medications.

- Blood samples (approximately 1 teaspoon of blood will be taken) to evaluate their blood
sugar levels. This can be done at a lab close to home. If the participant's doctor
thinks that their blood sugars need further monitoring, the participant may have
continued blood samples drawn to check their blood sugar weekly or daily past the first
cycle.

Every 2 cycles:

- Blood samples (approximately 1 teaspoon of blood will be taken) to evaluate the
participant's HgbA1C, a test that evaluates their blood sugar levels over a period of
time. This can be done at a lab close to home.

- CT scan or MRI of your chest, stomach area, and pelvis to see if the participant's
cancer is increasing, decreasing, or staying the same size. If the cancer is decreasing,
the participant's doctor may schedule the participant for another CT scan in about one
month to check it again.

- ECHO, a test to check the participant's heart's structure and function

At the end of the study:

- Recording of any health problems, including any side effects from the study drugs.

- List of medications taken since the last visit

- Physical examination (including measurement of the participant's vital signs, such as
blood pressure, breathing rate, heart rate, temperature, and weight.)

- Evaluation of the participant's performance status (their ability to carry on daily
activities).

- Blood samples (approximately 2-3 tablespoons of blood will be taken) to evaluate the
participant's blood counts, electrolytes, liver function, kidney function, blood sugar
level, and HgbA1C.

After the final dose of the study drug:

The investigator would like to keep track of the participant's medical condition for up to 3
years after the participant completes the study. The investigator would like to do this by
calling the participant on the telephone or seeing the participant in clinic for evaluation
of their status, disease and current therapy. Keeping in touch with the participant and
checking their condition routinely helps us look at the long-term effects of the research
study.

Inclusion Criteria:

- Recurrent or metastatic cervical cancer of any histology

- Measurable disease by RECIST 1.1.

- Prior Therapy:

- At least one prior chemotherapy regimen for management of cervical cancer.
Radiation-sensitizing chemotherapy will not be counted as a systemic chemotherapy
regimen

- Patients can have received one additional regimen for treatment

- No prior receipt of PI3K or RAS-ERK pathway inhibitors

- Age ≥ 18 years

- Life expectancy > 3 mos

- ECOG performance status ≤ 2

- Participants must have normal organ function as defined below:

- Absolute Neutrophil Count (ANC)≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Hemoglobin > 9.0/dL

- AST (SGOT) and ALT (SGPT) ≤ 2.5 × institutional ULN

- Total Bilirubin within normal institutional limits

- Albumin ≥ 2.5 g/dL

- Creatinine ≤ upper limit of institutional normal or creatinine clearance ≥ 50
mL/min/1.73 m2 for subjects with creatinine levels above institutional normal or ≥ 50
mL/min 24-hour creatinine clearance

- Normal LVEF

- Normal fasting Blood Glucose

- Availability of a formalin fixed paraffin embedded (FFPE) block of cancer tissue

- Normal blood pressure (systolic < 140 mmHg and diastolic < 90 mmHg)

- Women of childbearing potential must agree to use two forms of contraception (hormonal
or barrier method of birth control; abstinence) prior to study entry and for the
duration of study participation

- Toxicities of prior therapy (excepting alopecia) should be resolved to ≤ grade 1

- Ability to tolerate oral medications and no malabsorption

- Ability to sign an informed consent

Exclusion Criteria:

- No previous chemotherapy within 3 weeks (6 weeks for nitrosoureas or mitomycin C,) or
radiation therapy within 2 weeks prior to entering the study

- No use of investigational agents nor have participated in an investigational trial
within the past 4 weeks (or five half-lives whichever is shorter; with a minimum of 14
days from the last dose).

- Presence of active GI disease that could affect GI absorption or predispose a subject
to GI ulceration.

- Evidence of mucosal of internal bleeding

- Major surgery within the last 4 weeks

- No Type 1 diabetes; however, patients with Type 2 diabetes are eligible if diagnosed ≥
6 months prior to enrollment and if hemoglobin A1C (HbA1C) ≤ 8% at screening.

- Symptomatic or unstable brain metastases or asymptomatic and untreated but > 1 cm in
the longest dimension

- Symptomatic or untreated leptomeningeal or spinal cord compression.

- Individuals with a history of a different malignancy are ineligible except for the
following circumstances: the following cancers are eligible if diagnosed and treated
within the past 3 years: breast cancer in situ and basal cell or squamous cell
carcinoma of the skin, stage I colon carcinoma confined to a polyp.

- Any serious and/or unstable pre-existing medical disorders

- Known infection with HIV, Hepatitis B Virus, or Hepatitis C Virus

- Chronic use of drugs that are strong inhibitors or inducers of p450 CYP3A4

- known immediate or delayed hypersensitivity reaction or idiosyncrasy to study drugs

- History of interstitial lung disease or pneumonitis.

- Presence of cardiac metastases

- Subject with intra-cardiac defibrillators or pacemaker.

- History or current evidence / risk of retinal vein occlusion (RVO) or central serous
retinopathy (CSR)

- History of RVO or CSR, or predisposing factors to RVO or CSR

- Visible retinal pathology as assessed by ophthalmic exam

- History or evidence of cardiovascular risk including any of the following

- QTcF≥ 480 msec ( ≥ 500 msec for subject with bundle branch block)

- History or evidence of current clinically significant uncontrolled arrhythmias.
(Exception: controlled atrial fibrillation for >30 days prior to randomization)

- History of acute coronary syndromes (including myocardial infarction and unstable
angina), coronary angioplasty, or stenting within 6 months of study entry.

- Class II or higher congestive heart failure.