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

NCT01266954 | Completed Phase 1

• 1 other identifier: 113124
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• The amount of GSK2141795 in the blood (ng/ml) from baseline

  6 months

Secondary Outcomes (2)

• The net unidirectional uptake of FDG (Ki) from baseline

  6 months

• The change in size of tumor from baseline (RECIST Criteria)

  6 months

Study Arms (2)

Stage 1

EXPERIMENTAL

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

Drug: GSK2141795

Stage 2

EXPERIMENTAL

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

Drug: GSK2141795

Interventions

GSK2141795 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 1; Stage 2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

London, W12 0HS, United Kingdom

Location

Related Links

• Results for study 113124 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Neoplasms

Interventions

GSK2141795

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2010
• First Posted: December 24, 2010
• Study Start: June 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: November 9, 2017

Record last verified: 2017-11

Locations

GB (1)