Study to Assess the Pharmacokinetics and Pharmacodynamics of GSK461364 in Subjects With Non-Hodgkins Lymphoma
A Phase I Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of [GSK461364], a Polo-like Kinase 1 (PLK1) Inhibitor, in Adult Subjects With Advanced Solid Tumor or Non-Hodgkins Lymphoma
1 other identifier
interventional
41
1 country
3
Brief Summary
This is a first time in human study that is being done to determine the maximum tolerated dose and initial pharmacokinetic parameters of GSK461364, given by IV, in adult subjects with solid tumors and Non-Hodgkins lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2007
Typical duration for phase_1
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 16, 2007
CompletedFirst Submitted
Initial submission to the registry
September 27, 2007
CompletedFirst Posted
Study publicly available on registry
September 28, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 29, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
September 29, 2009
CompletedJune 26, 2017
June 1, 2017
2.1 years
September 27, 2007
June 23, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Plasma levels for GSK461364 will be taken at:Schedule 1:Day 1, 8, 15, & 22 for Cycle 1 and Day 1, 8 & 15 for subsequent cycles.Schedule 2:Day 1, 2, 8, 9, 15, & 16 for all cycles.Schedule 3:Day 1 to 5 for all cycles.
16 Days
Secondary Outcomes (1)
Safety will be evaluated by: - Physical exam at screen & then D1 for each cycle - 12 lead ECG & telemetry at screen & Wk 1 to 3 for Schedule 1 & 2, & Wk 1 & 2 (ECG only) for Schedule 3. - Lab tests & AE monitoring throughout the study.
16 Days
Study Arms (2)
Stage A
EXPERIMENTALStage A will identify maximum tolerated doses for either Schedule 1 - GSK461364 given once weekly on Day 1, 8 and 15 every 28 days; Schedule 2 - GSK 461364 given twice weekly Days 1, 2, 8, 9, 15 and 16; Schedule 3 Daily on Day 1 to Day 15 every 21 days.
Stage B
EXPERIMENTALEvaluate safety, PK, pharmacodynamic (PD) \& tumor response in expanded cohorts at the MTD for at least one schedule from Stage A.
Interventions
GSK461364 will be given intravenously as a 4 hour infusion in either a final volume of 500 or 1000 mLs. The starting dose for Stage A - Schedule 1 was 50 mg and doses were to be escalated as described in protocol until maximum tolerated dose established.
Eligibility Criteria
You may qualify if:
- Confirmed diagnosis of advanced solid tumor or Non-Hodgkins Lymphoma (excluding HIV-associated lymphoma) that has relapsed or is refractory to standard therapies
- At least 18 years of age
- Female who are of non-childbearing potential or who have a negative pregnancy test who uses approved contraception
- Male with a female partner of childbearing potential must have had a vasectomy or both are using approved contraception
- Lab values that are within range as described in the protocol
- Paraffin-embedded archival tumor tissue available for testing
- Signed written informed consent
You may not qualify if:
- Undergone major surgery or received anti-cancer therapy
- History of hemolytic anemia
- Clinical lab tests that are out of range as described in the protocol
- Females who are pregnant or lactating
- Significant heart problems
- Serious or unstable pre-existing medical or psychiatric condition
- Are not able to comply with the study protocol
- Use of prohibited medications
- Have low blood pressure
- Evidence of symptomatic or untreated central nervous system involvement and require corticosteroids or anti-epileptic meds
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (3)
GSK Investigational Site
Sutton, Surrey, SM2 5PT, United Kingdom
GSK Investigational Site
Belfast, Northern Ireland, BT9 7AB, United Kingdom
GSK Investigational Site
London, W12 0NN, United Kingdom
Related Publications (1)
Olmos D, Barker D, Sharma R, Brunetto AT, Yap TA, Taegtmeyer AB, Barriuso J, Medani H, Degenhardt YY, Allred AJ, Smith DA, Murray SC, Lampkin TA, Dar MM, Wilson R, de Bono JS, Blagden SP. Phase I study of GSK461364, a specific and competitive Polo-like kinase 1 inhibitor, in patients with advanced solid malignancies. Clin Cancer Res. 2011 May 15;17(10):3420-30. doi: 10.1158/1078-0432.CCR-10-2946. Epub 2011 Apr 1.
PMID: 21459796BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 27, 2007
First Posted
September 28, 2007
Study Start
August 16, 2007
Primary Completion
September 29, 2009
Study Completion
September 29, 2009
Last Updated
June 26, 2017
Record last verified: 2017-06
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.