Dose-finding Study in Platinum-Resistant Ovarian Cancer

* Dose-finding study of GSK2110183 administered in combination with carboplatin and paclitaxel to any subject with recurrent ovarian cancer.
* Safety and efficacy study of GSK2110183 administered in combination with carboplatin and paclitaxel to subjects with platinum-resistant ovarian cancer.

PKB116611 is an open-label Phase I/II study of the investigational drug GSK2110183 given in combination with carboplatin and paclitaxel to subjects with recurrent ovarian cancer. Phase I is a dose escalation evaluation of daily oral doses of GSK2110183 administered in combination with every 3 week carboplatin and paclitaxel to any subject with recurrent ovarian cancer. Phase II is a single arm evaluation of the clinical efficacy of the combination identified in Phase I to subjects with platinum-resistant ovarian cancer.

Eligibility Criteria:
Phase I Inclusion Criteria:

* Female, 18 years of age as of signing the informed consent form, capable of giving/complying with written informed consent
* Histologically or cytologically confirmed serous ovarian cancer (includes primary peritoneal and Fallopian tube)
* Negative serum pregnancy test in women of childbearing potential within 14 days of first dose of treatment, agree to use effective contraception during/after (6 months post dose of paclitaxel or 30 days post dose GSK2110183 whichever is longer)
* Performance Status score of 0-2 according to the ECOG scale.
* Able to swallow and retain oral medication
* Subjects diagnosed previously with Type 2 diabetes must have been diagnosed ≥ 6 months prior to enrollment
* Prior treatment-related toxicities (except for alopecia) must be ≤ Grade 1 according to NCI-CTCAE (Version 4.0 \[NCI, 2009\]) at the time of treatment allocation OR ≤ Grade 2 and stable for 4 weeks or longer at the time of screening evaluation. Exception: Subjects with peripheral neuropathy \>/= Grade 2 will NOT be eligible
* Adequate organ system function

Phase II Inclusion Criteria:

Cohort A

* Phase I criteria
* Documented complete or partial response by RECIST to at least 1 prior platinum-based therapy
* Progression defined by either (1) RECIST v1.1 criteria or (2) GCIG CA 125 criteria associated with symptoms necessitating treatment between 1 and 6 months of prior platinum-based therapy either in adjuvant or metastatic setting
* Subjects allowed to have a maximum of one non-platinum-based therapy between the onset of platinum resistance
* Must have radiologically measurable disease i.e. presenting with at least one measurable lesion per RECIST 1.1

Cohort B

* Phase I criteria
* Documented complete or partial response by RECIST to at least 1 prior platinum-based therapy
* Progression defined by either (1) RECIST v1.1 criteria or (2) GCIG CA 125 criteria associated with symptoms necessitating treatment while being treated with a regimen containing carboplatin and paclitaxel (or within 4 weeks of completing treatment)
* Subjects will be required to start on treatment within 8 weeks after the last infusion of chemotherapy and may not have had any other anti-cancer therapy in the intervening time
* Must have radiologically measurable disease i.e. presenting with at least one measurable lesion per RECIST 1.1
* Additional restrictions on number of prior therapies may be added to eligibility criteria based on emerging data

Exclusion Criteria:

* History of another malignancy (some exceptions may apply)
* Serious and/or unstable pre-existing medical or psychiatric disorder, or other conditions that could interfere with subject's safety, obtaining informed consent or compliance to the study procedures
* Current use of prohibited medication during treatment.
* Chemotherapy, immunotherapy, or other anti-cancer therapy within 14 days prior to the first dose study drug
* Radiotherapy prior to initiation of therapy (some exceptions may apply)
* Contraindications (identified by the investigator) to the doses of carboplatin and/or paclitaxel
* History of reduction in standard of care paclitaxel dose for peripheral neuropathy
* No known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to drugs similar or related to GSK2110183
* No known delayed hypersensitivity reaction or idiosyncratic reaction to drugs similar to carboplatin or paclitaxel (some exceptions may apply)
* Prior use of a drug that targets AKT including perifosine
* History of Type 1 diabetes
* Gastrointestinal disease or other condition that could affect absorption or predispose subject to gastrointestinal ulceration
* Mucosal or internal bleeding
* Major surgery within the last four weeks
* Infection requiring parenteral or oral anti-infective treatment
* Severe or uncontrolled systemic diseases
* Brain metastases and/or leptomeningeal disease
* QTcF interval ≥ 470 msecs
* Bundle branch block, pacemaker or clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd degree atrioventricular (AV) block
* History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty,stenting or bypass grafting within six months of Screening
* Class II, III or IV heart failure as defined by the NYHA functional classification system
* Pregnant or lactating female
* Malignancies related to HIV or solid organ transplant; history of known HIV, history of know HBV surface antigen positivity (subjects with documented laboratory evidence of HBV clearance may be enrolled) or positive HCV antibody