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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 1

Conditions: Solid Tumours

Treatments: Drug: GSK2141795

Study type: Interventional

Funder types: Industry

Identifiers

NCT01266954

113124

Details and patient eligibility

About

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.

Enrollment: 36 patients

Sex: Female

Ages: 18 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

---

36 participants in 2 patient groups

Stage 1

Experimental group

Description:

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

Treatment:

Drug: GSK2141795

Stage 2

Experimental group

Description:

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

Treatment:

Drug: GSK2141795