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

NCT ID: NCT01266954

Last Updated: 2017-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-01
• Study Completion Date: 2011-09-01

Brief Summary

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.

Conditions

Solid Tumours

Keywords

Cancer; 18F FDG; PK; PET; Positron Emission Tomography; PD; AKT Inhibitor; GSK2141795

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Stage 1

Three to six patients on a medium dose of GSK2141795 for four weeks

Group Type: EXPERIMENTAL

GSK2141795

Intervention Type: DRUG

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

Stage 2

Nine to eighteen subjects on a low, medium or high dose of GSK2141795 for four weeks

Group Type: EXPERIMENTAL

GSK2141795

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

London, , United Kingdom

Countries

United Kingdom

Other Identifiers

113124

Identifier Type: -

Identifier Source: org_study_id