A Phase I/IIa, First Time in human, open-label dose-escalation study of GSK2636771 in subjects with advanced solid tumors with PTEN deficiency

What is the purpose of this trial?

The study consists of a pre-screening period to determine if the subject’s tumor has phosphatase and tensin homolog (PTEN) deficiencies. Subjects then continue into the screening phase for Part 1, 2, or 3, as appropriate. In Part 1, 3 subjects will receive a single dose of 25 mg. After analysis of 24-hour pharmacokinetic (PK) samples, the subjects may receive continuous dosing or receive a single dose at another dose level.

In Part 2, subjects will be enrolled and dose escalation will occur in a 3+3 design.

Subjects will receive a single dose on Day 1, and then begin continuous daily dosing after collection of the 72-hour PK sample. Additional subjects may be enrolled at lower dose levels for assessment of pharmacodynamics. Once the maximum tolerated dose (MTD)/ maximum biologically effective dose (mBED) is determined, 12 subjects will be enrolled at that dose level and will have additional PK sampling, as well as urine and bile sampling for drug metabolite profiling. In Stage 1 of Part 3, 12 subjects will be enrolled in each of three individual tumor-specific cohorts and receive the MTD or mBED determined in Part 2. If ≥1 of 12 subjects in Stage 1 of each cohort has a confirmed response by Response Evaluation Criteria In Solid Tumors 1.1, an additional 18 subjects will be enrolled in Stage 2. If not, the cohort will be closed. All subjects in all parts/cohorts will receive daily dosing until withdrawal or unacceptable toxicity.

Participation Guidelines

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Sponsor:

GlaxoSmithKline

Dates:

February 2012

Last Updated:

Study HIC#:

1111009273

Clinicaltrials.gov ID: Yale0327984