“Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Subjects With Hormone Receptor-positive (HR+)/Human Epidermal Growth Factor Receptor 2 Negative (HER2-) Advanced or Metastatic Breast Cancer”
This is a combination Phase I and Phase II study, with an aim to evaluate the combination of GSK525762 and fulvestrant in women with HR+/HER2- advanced or metastatic breast cancer, who have disease that has progressed after prior treatment with at least one line of endocrine therapy. The objectives of the study are to first identify, in open-label single-arm Phase I, a recommended Phase II dose of GSK525762 that may be combined safely with fulvestrant. Phase I will follow a modified toxicity probability interval (mTPI) design, and a sentinel group will be evaluated first for dose-limiting toxicity and further expanded to collect additional safety data. This will be followed by a double-blind, randomized controlled Phase II, to identify the clinical activity of the two study treatments when given in combination. The composition of Phase II will be selected at the end of Phase I. Approximately, up to 140 subjects and 154 subjects will receive study treatment in Phase I and Phase II respectively. A completed subject will be one who is followed until death.
Drug - GSK525762
For Phase I, GSK525762 will be available as 5 mg and 25 mg oral tablets. Subjects will be initially dosed at 60 mg daily (Dose Level 1). Further subjects will be dosed based on the dose limiting toxicity rate, at a higher 'Dose Level 2' (or still higher, based on PK data), same 'Dose Level 1', or lower 'Dose Level 1'.
Drug - Placebo
Placebo will match GSK525762 tablets, and will be provided in Phase II only. Dosing will be done until unacceptable toxicity, progression of disease, death, or withdrawal of consent.
Drug - Fulvestrant
Fulvestrant will be supplied as a solution for injection in a prefilled syringe, at a strength of 250 milligrams (mg) per 5 milliliters (mL), for slow intramuscular (IM) injection into the buttocks. Two 5 mL injections (total 500 mg of fulvestrant) will be administered, one in each buttock, on Day 1, Day 15, Day 29, and once monthly thereafter.
A Phase I/II Dose Escalation and Expansion Study to Investigate the Safety, Pharmacokinetics, Pharmacodynamics and Clinical Activity of GSK525762 in Combination With Fulvestrant in Subjects With HR+/HER2- Advanced or Metastatic Breast Cancer