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

This study has been completed.
Sponsor:
Information provided by:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01266954
First received: October 21, 2010
Last updated: January 26, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Solid Tumours
Drug: GSK2141795
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • The amount of GSK2141795 in the blood (ng/ml) from baseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The net unidirectional uptake of FDG (Ki) from baseline [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The change in size of tumor from baseline (RECIST Criteria) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 9
Study Start Date: June 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01266954

Locations
United Kingdom
GSK Investigational Site
London, United Kingdom, W12 0HS
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
ClinicalTrials.gov Identifier: NCT01266954     History of Changes
Other Study ID Numbers: 113124
Study First Received: October 21, 2010
Last Updated: January 26, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Kingdom: Ethics Committee

Keywords provided by GlaxoSmithKline:
Cancer
18F FDG
PK
PET
Positron Emission Tomography
PD
AKT Inhibitor
GSK2141795

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders

ClinicalTrials.gov processed this record on September 15, 2014