Continuation Study of the Oral AKT Inhibitor GSK2110183
Condition: Cancer
Intervention: GSK2110183 (afuresertib)
Intervention description: Afuresertib is an oral, low nanomolar pan-AKT kinase inhibitor immediate release (IR) 50 mg or 75 mg tablets was to be taken orally with at least 200 mL of water, with or without food, in the morning.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: solid tumor; GSK2110183; hematologic malignancy; AKT inhibitor; cancer; safety

Summary:

      This multicenter, non-randomized, open-label, treatment continuation or 'rollover' study was
      designed to provide continued access to eligible subjects who had previously participated in
      a GSK2110183 study (parent study) sponsored by GlaxoSmithKline (GSK) or another research
      organization working on behalf of GSK. Eligible subjects had previously received clinical
      benefit from continued treatment and had to have ad an acceptable safety profile with
      GSK2110183. Subjects who had participated in a GSK2110183 combination study with an approved
      anti-cancer agent were also be eligible to enroll in this rollover study. Subjects who
      participated in combination studies with two investigational compounds (one being GSK2110183)
      were not eligible for this rollover study. Subjects were enrolled by cohort based on the
      duration and treatment received while in their parent study. Safety assessments (physical
      examinations, vital sign measurements, 12-lead electrocardiograms, echocardiograms or
      multiple-gated acquisition scans, clinical laboratory assessments and monitoring of adverse
      events) were evaluated during this study. Disease assessment were performed using local
      standard of care imaging practices and criteria appropriate for disease type and location.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Has provided signed informed consent for this study.

          -  Is currently participating in a GSK2110183 study (monotherapy or in combination with
             an approved anti-cancer agent) sponsored by GSK or by another research organization
             working on behalf of GSK.

          -  Currently benefitting from continued treatment and have an acceptable safety profile
             with GSK2110183 as determined by the investigator following previous treatment with
             GSK2110183 either as monotherapy or as part of a combination treatment regimen.

          -  Continued ability to swallow and retain orally administered study treatment(s) and
             does not have any clinically significant GI abnormalities that may alter absorption
             such as malabsorption syndrome or major resection of the stomach or bowels.

          -  Male subjects with a female partner of childbearing potential must be willing to
             continue practicing the same acceptable method of contraception as used in the parent
             study during the rollover study and for at least 16 weeks after the last dose of
             GSK2110183.

          -  Female subjects of childbearing potential, as defined in the parent study, must be
             willing to continue practicing the same acceptable method of contraception as used in
             the parent study during the rollover study and for at least 4 weeks after the last
             dose of GSK2110183.

          -  Female subjects of childbearing potential, as defined in parent study, must have
             negative serum pregnancy tests at the time of transition to this study.

          -  Maintain a performance status score of 0 to 2 according to the Eastern Cooperative
             Oncology Group (ECOG) scale

          -  Subjects with Type II diabetes are only allowed if their HbA1C is less than 8 percent
             at study entry.

          -  Have adequate organ system function

        Exclusion Criteria:

          -  Permanent discontinuation of GSK2110183 in the parent study due to toxicity or disease
             progression.

          -  Concomitant use of any type of anti-cancer treatment other than studied in the parent
             protocol.

          -  Local access to commercially available GSK2110183.

          -  Current use of a prohibitive medication(s)

          -  Current use of anticoagulants

          -  Any unresolved toxicity greater than Grade 2 , except for alopecia, (National Cancer
             Institute-Common Toxicity Criteria for Adverse Events [NCI-CTCAE], version 4.0) from
             parent study treatment at the time of transition to this study.

          -  History of HIV infection.

          -  Peripheral neuropathy greater than Grade 1

          -  History of hepatitis B or C infection (subjects with evidence of cleared hepatitis B
             are permitted).

          -  Evidence of severe or uncontrolled systemic diseases (e.g., unstable, or uncompensated
             respiratory, hepatic, renal, metabolic or cardiac disease).

          -  QTcF interval greater than 500 msecs at the time of transition to this study.

          -  Other clinically significant ECG abnormalities including 2nd degree (Type II) or 3rd
             degree atrioventricular (AV) block.

          -  Evidence of current Class II, III, or IV heart failure as defined by the New York
             Heart Association [NYHA, 1994] functional classification system at the time of
             transition to this study.

          -  Symptomatic or untreated leptomeningeal, CNS or brain metastases or spinal cord
             compression at the time of transition to this study.

          -  Lactating female or female who becomes pregnant prior to transition to this study.

          -  Previously diagnosed diabetes mellitus Type I. Subjects with Type II diabetes are
             allowed if entry criteria are fulfilled

          -  Any serious and/or unstable pre-existing medical, psychiatric disorder or other
             conditions at the time of transition to this study that could interfere with subject's
             safety, obtaining informed consent or compliance to the study procedures, in the
             opinion of the investigator or GSK Medical Monitor.