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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: GSK461364


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stage A<br>Stage 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. | Drug: GSK461364<br>* 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.<br>|
| Experimental: Stage B<br>Evaluate safety, PK, pharmacodynamic (PD) & tumor response in expanded cohorts at the MTD for at least one schedule from Stage A. | Drug: GSK461364<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, Non-Hodgkins Lymphoma, First time in human, PLK1 inhibitor, Advanced Solid Tumor, GSK461364