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 - Full Text View

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:

MedlinePlus related topics: Cancer Ovarian Cancer

Drug Information available for: Fludeoxyglucose F 18

U.S. FDA Resources

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:

Capable of giving written informed consent
Females of non-childbearing potential, 18 years or older with ovarian cancer
Histologically or cytologically confirmed diagnosis of PET-positive recurrent or persistent ovarian cancer
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)
Disease at least 2 cm suitable for assessment by imaging
Performance Status score of 0, 1 or 2 according to the Eastern Cooperative Oncology Group scale
Adequate organ systems function

Exclusion Criteria:

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

Contacts and Locations

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 May 22, 2013