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Dose-Escalation Study of GSK2126458 (FTIH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00972686
Recruitment Status : Completed
First Posted : September 7, 2009
Last Update Posted : May 9, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Solid Tumours Drug: GSK2126458 Phase 1

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 79 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Open-Label, Dose-Escalation Study of the Phosphoinositide 3-Kinase Inhibitor GSK2126458 in Subjects With Solid Tumors or Lymphoma
Actual Study Start Date : August 31, 2009
Actual Primary Completion Date : December 12, 2012
Actual Study Completion Date : March 31, 2015

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: GSK2126458
GSK2126458 is an experimental treatment for patients with cancer.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Metabolic profile in plasma at the maximum tolerated dose [ Time Frame: Subjects continue on study until disease progression or consent withdrawal ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00972686


Locations
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United States, California
GSK Investigational Site
San Francisco, California, United States, 94115
United States, New Jersey
GSK Investigational Site
New Brunswick, New Jersey, United States, 08901
United States, North Carolina
GSK Investigational Site
Chapel Hill, North Carolina, United States, 27599-7600
United States, Texas
GSK Investigational Site
Dallas, Texas, United States, 75246
GSK Investigational Site
Houston, Texas, United States, 77030
United States, Utah
GSK Investigational Site
Salt Lake City, Utah, United States, 84112-5550
United States, Washington
GSK Investigational Site
Seattle, Washington, United States, 98109
Netherlands
GSK Investigational Site
Amsterdam, Netherlands, 1066 CX
GSK Investigational Site
Utrecht, Netherlands, 3584 CX
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
More Information
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Additional Information:

Study Data/Documents: Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 112826
For additional information about this study please refer to the GSK Clinical Study Register

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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00972686    
Other Study ID Numbers: 112826
First Posted: September 7, 2009    Key Record Dates
Last Update Posted: May 9, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Keywords provided by GlaxoSmithKline:
solid tumors
lymphoma
Phosphoinositide 3-kinase inhibitor