Cancer
Conditions
Keywords
solid tumor, GSK2110183, hematologic malignancy, AKT inhibitor, cancer, safety
Brief 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.
Interventions
DRUGGSK2110183 (afuresertib)
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.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least One Adverse Events (AEs) | from the time of consent until the final study visit up to approx. 76 months | Adverse Events (AEs) includes Summary of adverse events, drug related AEs, Serious adverse events, adverse events leading to study treatment discontinuation and death. |
Countries
Australia, Canada, Ireland, South Korea, United States
Participant flow
Recruitment details
As this was a rollover study, there was no planned number of subjects. Eleven subjects were enrolled and analyzed in the study.
Pre-assignment details
There was no planned duration of treatment as this was a rollover study. The subjects could permanently discontinue the study treatment due to protocol deviation, adverse event, disease progression, withdrawal of consent, Investigator's discretion, lost to follow-up, termination of study or death.
Participants by arm
| Arm | Count |
|---|---|
| GSK2110183 (Afuresertib) All patients received the GSK2110183 (afuresertib) treatment | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Physician Decision | 8 |
Baseline characteristics
| Characteristic | GSK2110183 (Afuresertib) |
|---|---|
| Age, Continuous | 60.1 Years STANDARD_DEVIATION 14 |
| Race/Ethnicity, Customized Asian - East Asian heritage | 2 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European heritage | 9 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 2 / 11 |
Outcome results
Primary
Number of Participants With at Least One Adverse Events (AEs)
Adverse Events (AEs) includes Summary of adverse events, drug related AEs, Serious adverse events, adverse events leading to study treatment discontinuation and death.
Time frame: from the time of consent until the final study visit up to approx. 76 months
Population: The 'all treated subjects' population consisted of all subjects that received at least one dose of afuresertib in this rollover study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK2110183 (Afuresertib) | Number of Participants With at Least One Adverse Events (AEs) | 11 Participants |