Dose Escalation and Expansion Study of GSK525762 in Combination With Fulvestrant in Subjects With Estrogen Receptor Positive (ER+) Breast Cancer

Official Title

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 ER+ Breast Cancer

Summary:

This is a combination Phase I and Phase II study, with an aim to evaluate the combination of GSK525762 and fulvestrant in women with advanced or metastatic ER+ 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.

Trial Description

Primary Outcome:

  • Phase I: Number of subjects with adverse events (AE) and serious adverse events (SAE), for the determination of recommended Phase II dose of GSK525762
  • Phase I: Number of subjects with dose limiting toxicities (DLT)
  • Phase I: Number of subjects with dose reductions or delays, for the determination of recommended Phase II dose of GSK525762
  • Phase I: Overall response rate (ORR)
  • Phase I: Plasma concentration of GSK525762, for the determination of recommended Phase II dose of GSK525762
  • Phase I: Plasma concentration of fulvestrant, for the determination of recommended Phase II dose of GSK525762
  • Phase II: Progression free survival (PFS)
Secondary Outcome:
  • Phase I: Number of subjects with AEs or SAEs, as a measure of safety and tolerability
  • Phase I: Number of subjects with dose reductions or delays, as a measure of safety and tolerability
  • Phase I: Number of subjects withdrawn due to toxicity
  • Phase I: Number of subjects with abnormality in hematology parameters
  • Phase I: Number of subjects with abnormality in clinical chemistry parameters
  • Phase I: Number of subjects with abnormality in urinalysis parameters
  • Phase I: Number of subjects with abnormality in systolic and diastolic blood pressure
  • Phase I: Number of subjects with abnormality in pulse rate
  • Phase I: Number of subjects with abnormality in respiratory rate
  • Phase I: Number of subjects with abnormality in electrocardiogram (ECG)
  • Phase I: Number of subjects with abnormality in any cardiotoxicity parameters
  • Phase I: Number of subjects with abnormality in gastrointestinal parameters
  • Phase I: Disease control rate (DCR)
  • Phase I: Duration of response
  • Phase I: PFS
  • Phase I: Time to progression (TTP)
  • Phase I: Plasma concentration of GSK525762 and its metabolites, as a measure of drug exposure
  • Phase I: Plasma concentration of fulvestrant, as a measure of drug exposure
  • Phase I: Correlation between ESR1 mutations and clinical response, determined by targeted sequencing of tumour tissue
  • Phase II: Overall Survival (OS)
  • Phase II: TTP
  • Phase II: ORR
  • Phase II: DCR
  • Phase II: Plasma concentration of GSK525762 and its metabolites, as a measure of drug exposure
  • Phase II: Plasma concentration of fulvestrant, as a measure of drug exposure
  • Phase II: Correlation between ESR1 mutations and clinical response, determined by targeted sequencing of tumour tissue

View this trial on ClinicalTrials.gov

Interested in this trial?

Print this page and take it to your doctor to discuss your eligibilty and treatment options. Only your doctor can refer you to a clinical trial.

Resources

Canadian Cancer Society

These resources are provided in partnership with the Canadian Cancer Society