An Open-Label Phase I/II Study of GSK2110183 in Combination With Carboplatin and Paclitaxel in Subjects With Platinum-Resistant Ovarian Cancer
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:
- 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 within 6 months of prior
platinum-based therapy either in adjuvant or metastatic setting
- Subjects will be required to start on treatment within 8 months after the last
platinum-based therapy 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
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