Dose-Escalation Study of GSK2126458

Solid Tumours Clinical Trial

— FTIH  

Official title:

A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK2126458 in Subjects With Solid Tumors or Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00972686
• Other study ID #: 112826
• Status: Completed
• Phase: Phase 1
• First received: September 3, 2009
• Last updated: May 5, 2017
• Start date: August 31, 2009
• Est. completion date: March 31, 2015

Study information

• Verified date: May 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

P3K112826 is a Phase I, first-time-in-human dose escalation study in subjects with refractory malignancy. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.

Description:

This study is a Phase I, first-time-in-human dose escalation study in subjects with refractory solid tumors or lymphoma. The primary objective of this study is to determine the recommended Phase II dose of GSK2126458 based on safety and tolerability, pharmacokinetics, pharmacodynamics and preliminary evidence of clinical activity. Secondary objectives are to characterize the pharmacokinetics of GSK2126458; and to explore relationships between GSK2126458 pharmacokinetics, pharmacodynamics, response prediction biomarkers and clinical endpoints.

Subjects with solid tumors or lymphoma will initially receive oral GSK2126458 daily for 28 consecutive days in each 28 day cycle. Subjects may be dosed once or twice a day or may be dosed on an intermittent schedule depending on the safety, pharmacokinetic and pharmacodynamic results that become available as the study progresses. The starting dose will be 0.1 mg once a day. Expansion of some cohorts will be conducted to test tumor pharmacodynamics, further explore the toxicity profile and to look for preliminary evidence of activity in subjects with tumors with PIK3CA mutations. The recommended Phase II dose will be the lowest dose explored (at or below MTD) that maintains biologic activity with an acceptable tolerability profile.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 79
• Est. completion date: March 31, 2015
• Est. primary completion date: December 12, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically- or cytologically- confirmed diagnosis of solid tumor malignancy, or lymphoma

• Performance Status score of 0 or 1 according to the Eastern Cooperative Oncology Group (ECOG) scale.

• Female or male that is willing to take measures to avoid pregnancy in self or a partner, including abstinence, or double barrier method.

• Adequate organ system function

Exclusion Criteria:

• Use of an investigational anti-cancer medication within 28 days or 5 half-lives preceding the first dose of GSK2126458.

• Chemotherapy within the last 3 weeks (6 weeks for prior nitrosourea or mitomycin C

• Any major surgery, radiotherapy, or immunotherapy within the last 4 weeks.

• Prior use of any PI3K inhibitor.

• Current use of a prohibited medication or requires any of these medications during treatment with GSK2126458.

• Presence of an active gastrointestinal disease or other condition known to interfere significantly with the absorption, distribution, metabolism, or excretion of drugs.

• Unresolved toxicity greater than Grade 1 from previous anti-cancer therapy except alopecia.

• QTc interval = 480 msecs.

• History of acute coronary syndromes; Class II, III, or IV heart failure; stroke or subarachnoid hemorrhage.

• Systolic blood pressure (SBP) of =140 mmHg or diastolic blood pressure (DBP) of = 90mmHg.

• Previously diagnosed Type 1 diabetes mellitus. Subjects with Type 2 diabetes are prohibited in the dose escalation part of the study.

• Symptomatic or untreated leptomeningeal or brain metastases.

• Primary malignancy of the central nervous system.

Related Conditions & MeSH terms

• Solid Tumours

Intervention

Drug:
• GSK2126458
GSK2126458 is an experimental treatment for patients with cancer.

Locations

Country	Name	City	State
Netherlands	GSK Investigational Site	Amsterdam
Netherlands	GSK Investigational Site	Utrecht
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	New Brunswick	New Jersey
United States	GSK Investigational Site	Salt Lake City	Utah
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events (AEs) and changes in laboratory values and vital signs. Pharmacokinetic parameter values for GSK2126458, Change from baseline in protein markers in tumor and/or blood. Blood glucose and insulin levels. Tumor response, RECIST defined		Subjects continue on study until disease progression or consent withdrawal
Secondary	Metabolic profile in plasma at the maximum tolerated dose		Subjects continue on study until disease progression or consent withdrawal

External Links

•   Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
•   Results for study 112826 can be found on the GSK Clinical Study Register.