GSK1120212+GSK2141795 for Cervical Cancer

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.