Continuation Study of the Oral AKT Inhibitor GSK2110183

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01531894
• Collaborator: (none)
• Enrollment: 11
• Locations: 8
• Arm: 1
• Actual Duration (Months): 76.4
• Patients Per Site: 1.4
• Patients Per Site Per Month: 0

Study Details

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
• 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: Feb 8, 2012
• Actual Primary Completion Date: Jun 20, 2018
• Actual Study Completion Date: Jun 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 Names: ASB183

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Baltimore	Maryland	United States	21231
2	Novartis Investigative Site	Boston	Massachusetts	United States	02115
3	Novartis Investigative Site	New York	New York	United States	10029
4	Novartis Investigative Site	New York	New York	United States	10065
5	Novartis Investigative Site	Melbourne	Victoria	Australia	3004
6	Novartis Investigative Site	Toronto	Ontario	Canada	M5G 1Z6
7	Novartis Investigative Site	Galway		Ireland
8	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)

• Study Protocol - Mar 31, 2016
• Statistical Analysis Plan - Nov 27, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01531894
• Other Study ID Numbers: 115131; 2014-002041-22
• First Posted: Feb 13, 2012
• Last Update Posted: Jul 9, 2019
• Last Verified: Jun 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: solid tumor; GSK2110183; hematologic malignancy; AKT inhibitor; cancer; safety

Study Results

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 Detail	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.

Arm/Group Title	GSK2110183 (Afuresertib)
Arm/Group Description	All patients received the GSK2110183 (afuresertib) treatment
Period Title: Overall Study
STARTED	11
COMPLETED	2
NOT COMPLETED	9

Baseline Characteristics

Arm/Group Title	GSK2110183 (Afuresertib)
Arm/Group Description	All patients received the GSK2110183 (afuresertib) treatment
Overall Participants	11
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.1 (14.00)
Sex: Female, Male (Count of Participants)
Female	8 72.7%
Male	3 27.3%
Race/Ethnicity, Customized (Number) [Number]
Asian - East Asian heritage	2 18.2%
White - White/Caucasian/European heritage	9 81.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With at Least One Adverse Events (AEs)
Description	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

Outcome Measure Data

Analysis Population Description

The 'all treated subjects' population consisted of all subjects that received at least one dose of afuresertib in this rollover study.

Arm/Group Title	GSK2110183 (Afuresertib)
Arm/Group Description	All patients received the GSK2110183 (afuresertib) treatment
Measure Participants	11
Count of Participants [Participants]	11 100%

Adverse Events

Time Frame	Adverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 2239 days.
Adverse Event Reporting Description	All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of about 76 months.
Arm/Group Title	All Patients
Arm/Group Description	All patients received the GSK2110183 (afuresertib) treatment
All Cause Mortality
	All Patients
	Affected / at Risk (%)	# Events
Total	1/11 (9.1%)
Serious Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	2/11 (18.2%)
Gastrointestinal disorders
Gastritis	1/11 (9.1%)
Infections and infestations
Pneumonia	1/11 (9.1%)
Other (Not Including Serious) Adverse Events
	All Patients
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Anaemia	1/11 (9.1%)
Lymphopenia	1/11 (9.1%)
Neutropenia	2/11 (18.2%)
Cardiac disorders
Palpitations	1/11 (9.1%)
Ear and labyrinth disorders
Ear discomfort	1/11 (9.1%)
Gastrointestinal disorders
Abdominal discomfort	1/11 (9.1%)
Abdominal distension	1/11 (9.1%)
Diarrhoea	7/11 (63.6%)
Gastrooesophageal reflux disease	1/11 (9.1%)
Large intestine polyp	1/11 (9.1%)
Nausea	1/11 (9.1%)
Oesophageal discomfort	1/11 (9.1%)
Oesophageal pain	1/11 (9.1%)
Tooth disorder	1/11 (9.1%)
Vomiting	2/11 (18.2%)
General disorders
Asthenia	1/11 (9.1%)
Chest discomfort	2/11 (18.2%)
Fatigue	5/11 (45.5%)
Oedema	1/11 (9.1%)
Oedema peripheral	1/11 (9.1%)
Peripheral swelling	1/11 (9.1%)
Infections and infestations
Chronic sinusitis	1/11 (9.1%)
Conjunctivitis	1/11 (9.1%)
Helicobacter infection	1/11 (9.1%)
Nasopharyngitis	1/11 (9.1%)
Respiratory tract infection	1/11 (9.1%)
Sinusitis	1/11 (9.1%)
Tooth infection	1/11 (9.1%)
Upper respiratory tract infection	2/11 (18.2%)
Urinary tract infection	2/11 (18.2%)
Metabolism and nutrition disorders
Decreased appetite	2/11 (18.2%)
Hyperglycaemia	1/11 (9.1%)
Musculoskeletal and connective tissue disorders
Foot deformity	1/11 (9.1%)
Muscle spasms	1/11 (9.1%)
Temporomandibular joint syndrome	1/11 (9.1%)
Nervous system disorders
Ageusia	1/11 (9.1%)
Anosmia	1/11 (9.1%)
Dizziness	1/11 (9.1%)
Paraesthesia	1/11 (9.1%)
Renal and urinary disorders
Micturition urgency	1/11 (9.1%)
Nephrolithiasis	1/11 (9.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/11 (27.3%)
Dyspnoea	1/11 (9.1%)
Epistaxis	2/11 (18.2%)
Nasal congestion	2/11 (18.2%)
Skin and subcutaneous tissue disorders
Erythema	1/11 (9.1%)
Pruritus	2/11 (18.2%)
Pruritus generalised	1/11 (9.1%)
Rash	1/11 (9.1%)
Skin ulcer	1/11 (9.1%)
Vascular disorders
Hypertension	1/11 (9.1%)
Raynaud's phenomenon	1/11 (9.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.