Clinical trial NCT01531894: Continuation Study of the Oral AKT Inhibitor GSK2110183
Official title: An Open Label Continuation Study of the Oral AKT Inhibitor GSK2110183 in Subjects With Solid Tumors and Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer
Keywords: solid tumor
GSK2110183
hematologic malignancy
AKT inhibitor
cancer
safety
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-02-13
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With at Least One Adverse Events (AEs)
timeFrame: from the time of consent until the final study visit up to approx. 76 months
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Novartis Investigative Site
state: Maryland
city: Boston
country: United States
facility: Novartis Investigative Site
state: Massachusetts
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: New York
country: United States
facility: Novartis Investigative Site
state: New York
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Galway
country: Ireland
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: