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A Study of GSK2256098 and Trametinib in Advanced Pancreatic Cancer

Primary Purpose

Pancreatic Cancer, Adenocarcinoma

Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
GSK2256098
Trametinib
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female, 18 years or older, able to give written consent
  • Pancreatic adenocarcinoma that is not responsive to standard therapies or for which there is no approved or curative therapy or for patients who refuse standard therapy
  • Have clinical, radiographic, or serologic progression after one prior line of chemotherapy for advanced disease. Patients who have received two or more prior lines of chemotherapy for advanced disease are not eligible.
  • Performance Status score of 0 or 1
  • Measureable disease by RECIST version 1.1
  • Able to swallow and retain oral medication
  • Have malignant disease that is amenable to biopsy and agree to collection of mandatory tumor biopsy samples.
  • Agrees to use contraception
  • Not pregnant
  • Adequate organ system function

Exclusion Criteria:

  • Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including investigational drugs within 28 days or 5 half lives. No prior MEK inhibitor, RAF inhibitors or a FAK inhibitors
  • Current use of a prohibited medication
  • Unresolved toxicity greater than Grade 1 from previous anticancer therapy unless the ongoing toxicity will not introduce additional risk factors and will not interfere with the study procedures.
  • Presence of active GI disease or other condition that could affect gastrointestinal absorption or predisposed to GI ulceration
  • Evidence of mucosal or internal bleeding
  • Anticoagulation with warfarin
  • Major surgery within the last four weeks
  • Malignancies related to HIV or HBV/HCV
  • Known active infection requiring parenteral or oral anti-infective treatment
  • Leptomeningeal disease.
  • Brain metastases
  • QTcF interval ≥ 480 msecs
  • History or evidence of current clinically significant uncontrolled arrhythmias
  • History of acute coronary syndromes, myocardial infarction, coronary angioplasty, or stenting or bypass grafting within six months of screening.
  • Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
  • Other clinically significant ECG abnormalities
  • Intra-cardiac defibrillators.
  • Presence of cardiac metastases.
  • Serious or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety or providing informed consent.
  • Known immediate or delayed hypersensitivity to any of the components of the study treatment(s).
  • Evidence of severe or uncontrolled systemic diseases
  • Pregnant or lactating
  • History of retinal vein occlusion
  • History of interstitial lung disease or pneumonitis

Sites / Locations

  • Juravinski Cancer Center
  • London Regional Cancer Centre
  • The Ottawa Hospital Cancer Centre
  • Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

GSK2256098 and Trametinib

Arm Description

GSK2256098, orally, at 0.375 or 0.5 mg, once daily, continuously every 28 day cycles. Trametinib, orally at 250 mg or 500 mg, twice daily, continuously every 28 day cycles.

Outcomes

Primary Outcome Measures

Percentage of patients who experience complete response, partial response, or stable disease

Secondary Outcome Measures

Adverse events based on frequency and proportion of total patients, by system organ class and preferred term.
Percentage of patients achieving either a complete or partial tumor response.
Interval between the date of randomization and the earliest date of disease progression or death due to any cause
Interval between the first date of CR or PR and the earliest date of disease progression or death due to any cause.

Full Information

First Posted
April 23, 2015
Last Updated
October 31, 2022
Sponsor
University Health Network, Toronto
Collaborators
GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT02428270
Brief Title
A Study of GSK2256098 and Trametinib in Advanced Pancreatic Cancer
Official Title
Molecular Basket Trial In Multiple Malignancies With Common Target Pathway Aberrancies: A Phase II Trial of GSK2256098 and Trametinib in Patients With Advanced Pancreatic Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
April 2016 (undefined)
Primary Completion Date
June 2017 (Actual)
Study Completion Date
October 27, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
GlaxoSmithKline

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase 2 study (the second phase in testing a new drug or combination to see how effect the drug or combination is) of investigational drugs GSK2256098 and Trametinib. The purpose of the study is to evaluate the antitumor activity of GSK2256098 and Trametinib in patients with advanced pancreatic cancer.
Detailed Description
Trametinib is a drug that works by binding to and blocking certain proteins called mitogen-activated protein kinase kinase (MEK) 1 and MEK2 from working. MEK1 and MEK2 are important proteins that contribute to the growth of cancer cells. GSK2256098 is a drug that blocks a protein called focal adhesion kinase-1 (FAK) which is an important protein that contribute to the growth of cancer cells.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer, Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
GSK2256098 and Trametinib
Arm Type
Experimental
Arm Description
GSK2256098, orally, at 0.375 or 0.5 mg, once daily, continuously every 28 day cycles. Trametinib, orally at 250 mg or 500 mg, twice daily, continuously every 28 day cycles.
Intervention Type
Drug
Intervention Name(s)
GSK2256098
Intervention Description
Small molecule inhibitor of focal adhesion kinase (FAK)
Intervention Type
Drug
Intervention Name(s)
Trametinib
Other Intervention Name(s)
Mekinist
Intervention Description
Allosteric inhibitor of mitogen-activated extracellular signal-regulated kinase (MEK)1 and MEK2 activation and kinase activity.
Primary Outcome Measure Information:
Title
Percentage of patients who experience complete response, partial response, or stable disease
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Adverse events based on frequency and proportion of total patients, by system organ class and preferred term.
Time Frame
2 years
Title
Percentage of patients achieving either a complete or partial tumor response.
Time Frame
2 years
Title
Interval between the date of randomization and the earliest date of disease progression or death due to any cause
Time Frame
2 years
Title
Interval between the first date of CR or PR and the earliest date of disease progression or death due to any cause.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female, 18 years or older, able to give written consent Pancreatic adenocarcinoma that is not responsive to standard therapies or for which there is no approved or curative therapy or for patients who refuse standard therapy Have clinical, radiographic, or serologic progression after one prior line of chemotherapy for advanced disease. Patients who have received two or more prior lines of chemotherapy for advanced disease are not eligible. Performance Status score of 0 or 1 Measureable disease by RECIST version 1.1 Able to swallow and retain oral medication Have malignant disease that is amenable to biopsy and agree to collection of mandatory tumor biopsy samples. Agrees to use contraception Not pregnant Adequate organ system function Exclusion Criteria: Chemotherapy, radiotherapy, immunotherapy, or other anti-cancer therapy including investigational drugs within 28 days or 5 half lives. No prior MEK inhibitor, RAF inhibitors or a FAK inhibitors Current use of a prohibited medication Unresolved toxicity greater than Grade 1 from previous anticancer therapy unless the ongoing toxicity will not introduce additional risk factors and will not interfere with the study procedures. Presence of active GI disease or other condition that could affect gastrointestinal absorption or predisposed to GI ulceration Evidence of mucosal or internal bleeding Anticoagulation with warfarin Major surgery within the last four weeks Malignancies related to HIV or HBV/HCV Known active infection requiring parenteral or oral anti-infective treatment Leptomeningeal disease. Brain metastases QTcF interval ≥ 480 msecs History or evidence of current clinically significant uncontrolled arrhythmias History of acute coronary syndromes, myocardial infarction, coronary angioplasty, or stenting or bypass grafting within six months of screening. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system. Other clinically significant ECG abnormalities Intra-cardiac defibrillators. Presence of cardiac metastases. Serious or unstable pre-existing medical, psychiatric, or other condition that could interfere with patient's safety or providing informed consent. Known immediate or delayed hypersensitivity to any of the components of the study treatment(s). Evidence of severe or uncontrolled systemic diseases Pregnant or lactating History of retinal vein occlusion History of interstitial lung disease or pneumonitis
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Philippe Bedard, M.D.
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Juravinski Cancer Center
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8V 5C2
Country
Canada
Facility Name
London Regional Cancer Centre
City
London
State/Province
Ontario
Country
Canada
Facility Name
The Ottawa Hospital Cancer Centre
City
Ottawa
State/Province
Ontario
Country
Canada
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

A Study of GSK2256098 and Trametinib in Advanced Pancreatic Cancer

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