Continuation Study of the Oral AKT Inhibitor GSK2110183

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: GSK2110183 (afuresertib)

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Novartis Investigative Site
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z6
      • Novartis Investigative Site
• Ireland
  • Galway, Ireland
    • Novartis Investigative Site
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Novartis Investigative Site
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Novartis Investigative Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10029
      • Novartis Investigative Site
    • New York, New York, United States, 10065
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK2110183 (afuresertib); All patients received the GSK2110183 (afuresertib) treatment	Drug: GSK2110183 (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.; Other Names: ASB183

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	from the time of consent until the final study visit up to approx. 76 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2012
• Primary Completion (Actual): June 20, 2018
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: February 9, 2012
• First Submitted That Met QC Criteria: February 9, 2012
• First Posted (Estimate): February 13, 2012

Study Record Updates

• Last Update Posted (Actual): July 9, 2019
• Last Update Submitted That Met QC Criteria: June 20, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: safety; cancer; hematologic malignancy; solid tumor; AKT inhibitor; GSK2110183
• Other Study ID Numbers: 115131; 2014-002041-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No