Dose-Escalation Study of GSK2126458 (FTIH)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00972686
First received: September 3, 2009
Last updated: August 7, 2014
Last verified: August 2014

September 3, 2009
August 7, 2014
November 2009
December 2012   (final data collection date for primary outcome measure)
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 [ Time Frame: Subjects continue on study until disease progression or consent withdrawal ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00972686 on ClinicalTrials.gov Archive Site
Metabolic profile in plasma at the maximum tolerated dose [ Time Frame: Subjects continue on study until disease progression or consent withdrawal ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Dose-Escalation Study of GSK2126458
A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK2126458 in Subjects With Solid Tumors or Lymphoma

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.

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.

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Tumours
Drug: GSK2126458
GSK2126458 is an experimental treatment for patients with cancer.
Experimental: GSK2126458
GSK2126458 will be dosed continuously (every day) for the duration a 28 day cycle. The 28 day cycles will continue until the subjects withdraw from the study.
Intervention: Drug: GSK2126458
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
150
December 2015
December 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Netherlands
 
NCT00972686
112826
Not Provided
GlaxoSmithKline
GlaxoSmithKline
Not Provided
Study Director: GSK Clinical Trials GlaxoSmithKline
GlaxoSmithKline
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP