Solid Tumours
Conditions
Keywords
Cancer, 18F FDG, PK, PET, Positron Emission Tomography, PD, AKT Inhibitor, GSK2141795
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.
Interventions
DRUGGSK2141795
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
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The amount of GSK2141795 in the blood (ng/ml) from baseline | 6 months |
Secondary
| 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 |
Countries
United Kingdom
Outcome results
None listed