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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 41
- Locations
- 1
- Primary Endpoint
- 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.
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Stage A
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.
Intervention: GSK461364 (Drug)
Stage B
Evaluate safety, PK, pharmacodynamic (PD) & tumor response in expanded cohorts at the MTD for at least one schedule from Stage A.
Intervention: GSK461364 (Drug)
Outcomes
Primary Outcomes
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.
Time Frame: 16 Days
Secondary Outcomes
- 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)