An Open Label Study To Investigate the Pharmacokinetics and Pharmacodynamics of Repeat Escalating Doses of the Oral AKT Inhibitor GSK2141795 by 18F FDG PET Analysis in Subjects With Ovarian Cancer

The purpose of this study is to explore the potential dose response relationship between the pharmacokinetics of GSK2141795 and [18F] FDG PET pharmacodynamic markers of glucose metabolism in tumor tissue. Three to six subjects will be enrolled in each cohort and dosed with repeat escalating doses of GSK2141795. [18F] FDG PET imaging and optional tumor biopsies will be done prior to initiation of dosing and sequentially at select time points during the first five weeks of dosing. The maximal dose of a given schedule evaluated in this study will not exceed the maximal tolerated dose established in the first-time-in-human trial PCS112689 for the same schedule.

Study Overview

• Status: Completed
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: GSK2141795

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W12 0HS
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Capable of giving written informed consent
2. Females of non-childbearing potential, 18 years or older with ovarian cancer
3. Histologically or cytologically confirmed diagnosis of PET-positive recurrent or persistent ovarian cancer
4. Histologically or cytologically confirmed diagnosis of PET-positive recurrent or persistent uterine or gastro-oesophageal tumors (these tumor types will only be included if there is poor enrollment of patients with ovarian cancer)
5. Disease at least 2 cm suitable for assessment by imaging
6. Performance Status score of 0, 1 or 2 according to the Eastern Cooperative Oncology Group scale
7. Adequate organ systems function

Exclusion Criteria:

1. Chemotherapy, radiotherapy, or immunotherapy within 28 days prior to the first dose of GSK2141795
2. Use of an investigational anti-cancer drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of GSK2141795
3. Current use of a prohibited medication
4. Anticoagulants at therapeutic doses are permitted only after consultation with the GSK Medical Monitor
5. Presence of active gastrointestinal disease or other condition that could affect gastrointestinal absorption
6. Any major surgery within the last four weeks of screening
7. Unresolved toxicity greater than or equal to Grade 2 from previous anti-cancer therapy
8. Previously diagnosed diabetes mellitus
9. Current use of oral corticosteroids, with the exception of inhaled or topical corticosteroids
10. Any serious or unstable pre-existing medical, psychiatric, or other condition
11. Symptomatic or untreated CNS metastases or leptomeningeal involvement
12. Evidence of severe or uncontrolled systemic diseases
13. QTc interval ≥ 470 msecs
14. Other clinically significant ECG abnormalities
15. History of myocardial infarction, acute coronary syndromes
16. Class III or IV heart failure
17. Pregnant or Lactating patients
18. History of hepatitis B or C or HIV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1; Three to six patients on a medium dose of GSK2141795 for four weeks	Drug: GSK2141795; GSK2141795 is an oral, low nanomolar pan-AKT kinase inhibitor that demonstrates activity in hematologic and solid tumor cell lines. It also delays tumor growth in a dose dependent manner in solid tumor xenograft mouse models
Experimental: Stage 2; Nine to eighteen subjects on a low, medium or high dose of GSK2141795 for four weeks	Drug: GSK2141795; GSK2141795 is an oral, low nanomolar pan-AKT kinase inhibitor that demonstrates activity in hematologic and solid tumor cell lines. It also delays tumor growth in a dose dependent manner in solid tumor xenograft mouse models

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The amount of GSK2141795 in the blood (ng/ml) from baseline	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
The net unidirectional uptake of FDG (Ki) from baseline	6 months
The change in size of tumor from baseline (RECIST Criteria)	6 months

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: October 21, 2010
• First Submitted That Met QC Criteria: December 23, 2010
• First Posted (Estimate): December 24, 2010

Study Record Updates

• Last Update Posted (Actual): November 9, 2017
• Last Update Submitted That Met QC Criteria: November 7, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Cancer; PET; Positron Emission Tomography; PK; PD; AKT Inhibitor; 18F FDG; GSK2141795
• Other Study ID Numbers: 113124