Study to Assess the Pharmacokinetics and Pharmacodynamics of GSK461364 in Subjects With Non-Hodgkins Lymphoma

Lymphoma, Non-Hodgkin Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536835
• Other study ID #: PLK107427
• Status: Completed
• Phase: Phase 1
• First received: September 27, 2007
• Last updated: June 23, 2017
• Start date: August 16, 2007
• Est. completion date: September 29, 2009

Study information

• Verified date: June 2017
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: September 29, 2009
• Est. primary completion date: September 29, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• GSK461364
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.

Locations

Country	Name	City	State
United Kingdom	GSK Investigational Site	Belfast, Northern Ireland
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Sutton	Surrey

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Country where clinical trial is conducted

United Kingdom, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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

External 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.
•   Results for study 107427 can be found on the GSK Clinical Study Register.