Continuation Study of the Oral AKT Inhibitor GSK2110183

• ClinicalTrials.gov Identifier: NCT01531894
• Recruitment Status: Completed
• First Posted: February 13, 2012
• Results First Posted: July 9, 2019
• Last Update Posted: July 9, 2019
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer	Drug: GSK2110183 (afuresertib)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open Label Continuation Study of the Oral AKT Inhibitor GSK2110183 in Subjects With Solid Tumors and Hematologic Malignancies
• Actual Study Start Date: February 8, 2012
• Actual Primary Completion Date: June 20, 2018
• Actual Study Completion Date: June 20, 2018

Arms and Interventions

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 Name: ASB183

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With at Least One Adverse Events (AEs) [ Time Frame: 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.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

United States, Maryland

Novartis Investigative Site

Baltimore, Maryland, United States, 21231

United States, Massachusetts

Novartis Investigative Site

Boston, Massachusetts, United States, 02115

United States, New York

Novartis Investigative Site

New York, New York, United States, 10029

Novartis Investigative Site

New York, New York, United States, 10065

Australia, Victoria

Novartis Investigative Site

Melbourne, Victoria, Australia, 3004

Canada, Ontario

Novartis Investigative Site

Toronto, Ontario, Canada, M5G 1Z6

Ireland

Novartis Investigative Site

Galway, Ireland

Korea, Republic of

Novartis Investigative Site

Seoul, Korea, Republic of, 110-744

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):

Study Protocol  [PDF] March 31, 2016

Statistical Analysis Plan  [PDF] November 27, 2017

More Information

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01531894
• Other Study ID Numbers: 115131; 2014-002041-22 ( EudraCT Number )
• First Posted: February 13, 2012
• Results First Posted: July 9, 2019
• Last Update Posted: July 9, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

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.

• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

solid tumor; GSK2110183; hematologic malignancy; AKT inhibitor; cancer; safety