Continuation Study of the Oral AKT Inhibitor GSK2110183

Status:	Completed
Conditions:	Cancer
Therapuetic Areas:	Oncology
Healthy:	No
Age Range:	18 - 80
Updated:	7/14/2018
Start Date:	February 8, 2012
End Date:	June 20, 2018

An Open Label Continuation Study of the Oral AKT Inhibitor GSK2110183 in Subjects With Solid Tumors and Hematologic Malignancies

GSK2110183 is an orally administered, pan-AKT kinase inhibitor that has demonstrated
nonclinical activity in hematologic as well as solid tumor cell lines and xenograft models.
In the First Time In Human (FTIH) trial, monotherapy with GSK2110183 dosed orally, once daily
has shown encouraging activity in subjects with hematologic malignancies. This multicenter,
non-randomized, open-label, treatment continuation or 'rollover' study is designed to provide
continued access to eligible subjects who have previously participated in a GSK2110183 study
(parent study) sponsored by GlaxoSmithKline (GSK) or another research organization working on
behalf of GSK. Eligible subjects must be receiving clinical benefit from continued treatment
and have an acceptable safety profile with GSK2110183. Subjects who have participated in a
GSK2110183 combination study with an approved anti-cancer agent will also be eligible to
enroll in this rollover study. Subjects who participated in combination studies with two
investigational compounds (one being GSK2110183) will not be eligible for this rollover
study. Subjects will be 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) will be evaluated during this study.
Disease assessment will be performed using local standard of care imaging practices and
criteria appropriate for disease type and location.

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.

We found this trial at

sites

Novartis

230 Park Avenue, 21st Floor
New York, New York 10169

1-888-669-6682)