Dose-finding Study in Platinum-Resistant Ovarian Cancer

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
• •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