Clinical trial NCT00536835: Study to Assess the Pharmacokinetics and Pharmacodynamics of GSK461364 in Subjects With Non-Hodgkins Lymphoma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Keywords: Non-Hodgkins Lymphoma
Cancer
First time in human
PLK1 inhibitor
Advanced Solid Tumor
GSK461364
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2007-09-28
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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.
timeFrame: 16 Days
Secondary outcomes:
measure: 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.
timeFrame: 16 Days
Other outcomes:
Locations:
city: Sutton
country: United Kingdom
facility: GSK Investigational Site
state: Surrey
city: Belfast, Northern Ireland
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.