Dose-Escalation Study of GSK2126458 (FTIH)

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.

Study Overview

• Status: Completed
• Conditions: Solid Tumours
• Intervention / Treatment: Drug: GSK2126458

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 Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • GSK Investigational Site
  • Utrecht, Netherlands, 3584 CX
    • GSK Investigational Site
• United States
  • California
    • San Francisco, California, United States, 94115
      • GSK Investigational Site
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7600
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75246
      • GSK Investigational Site
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84112-5550
      • GSK Investigational Site
  • Washington
    • Seattle, Washington, United States, 98109
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
Metabolic profile in plasma at the maximum tolerated dose	Subjects continue on study until disease progression or consent withdrawal

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 31, 2009
• Primary Completion (ACTUAL): December 12, 2012
• Study Completion (ACTUAL): March 31, 2015

Study Registration Dates

• First Submitted: September 3, 2009
• First Submitted That Met QC Criteria: September 4, 2009
• First Posted (ESTIMATE): September 7, 2009

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 5, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: lymphoma; solid tumors; Phosphoinositide 3-kinase inhibitor
• Other Study ID Numbers: 112826

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.

Study Data/Documents

1. Statistical Analysis Plan
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 112826
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register