GO39932

• Research type

  Research Study

• Full title

  A PHASE Ia/Ib, MULTICENTER, OPEN-LABEL, DOSE ESCALATION, DOSE EXPANSION STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, AND ACTIVITY OF GDC 9545 ALONE OR IN COMBINATION WITH PALBOCICLIB AND/OR LHRH AGONIST IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC ESTROGEN RECEPTORPOSITIVE BREAST CANCER

• IRAS ID

  239952

• Contact name

  Turner Nicholas

• Contact email

  Nick.Turner@icr.ac.uk

• Eudract number

  2017-002083-41

• Clinicaltrials.gov Identifier

  NCT03332797

• Duration of Study in the UK

  1 years, 3 months, 1 days

• Research summary

  GDC-9545 is an investigational new drug designed to block the female sex hormones that contribute to cancer progression. When mice with breast cancer were given GDC-9545, GDC-9545 slowed or stopped the cancer growth by blocking the female sex hormones. It is believed GDC-9545 will work the same way in humans and may help stop or slow the growth of breast cancer cells.

  This study aims to evaluate the safety (side effects) and look for any anti cancer activity of GDC-9545 alone or in combination with palbociclib and/or an LHRH agonist in women with advanced breast cancer.

  This is an open label study where patients will be enrolled in two stages: a dose escalation stage and an expansion stage.
  Dose- Escalation Study:

  Up to 30 patients maybe enrolled in the dose-escalation portion of the study. Patients will be treated with different doses of GDC-9545 alone, starting with a low dose, and slowly increasing the dose as new patients take part in the study until the highest dose that does not cause bad side effects is identified. Up to 7 patients may be enrolled at each dose level of GDC-9545 alone that is considered safe while the next dose level is being tested. Up to 26 patients will be treated with GDC-9545 in combination with palbociclib

  The dosing information learned from the dose escalation portion of the study will be used to determine the dose level of GDC 9545 used for the dose-expansion portion of the study.

  Dose-Expansion Study:
  Approximately 100 patients, who include postmenopausal as well as pre- and perimenopausal women, may be enrolled in the dose-expansion stage. This stage will consist of a screening period, a treatment period, and a safety follow-up period.
  Up to 6 cohorts may be enrolled as follows:
  • Cohort A1: Up to approximately 30 postmenopausal women to be treated with single-agent  MAD/MTD GDC-9545 (Dose 1)
  • Cohort A2: Up to approximately 10 pre- or perimenopausal women to be treated with  MAD/MTD GDC-9545 (Dose 1) plus LHRH agonist
  • Cohort A3: Up to approximately 30 postmenopausal women to be treated with single-agent  MAD/MTD GDC-9545 (Dose 2)
  • Cohort A4: Up to approximately 10 pre- or perimenopausal women to be treated with  MAD/MTD GDC-9545 (Dose 2) plus LHRH agonist
  • Cohort B1: Up to approximately 10 postmenopausal women to be treated with GDC-9545 at  MAD/MTD plus 125 mg palbociclib
  • Cohort B2: Up to approximately 10 pre- or perimenopausal women to be treated with GDC-9545 at  MAD/MTD plus 125 mg palbociclib plus LHRH agonist

  GDC-9545 is taken as a tablet and will be available in two different strengths, 10-mg and 50-mg.

  GDC-9545 will be administered (oral) daily starting at 10 mg dosing and may increase with each escalation cohort the participant is assigned to.
  Palbociclib will be administered (oral) daily at the label-recommended dose of 125 mg.

  The total length of the study, from screening of the first patient to the end of the study, is expected to be approximately 21 months

  This study is sponsored by Genentech. Approximately 100 patients will participate in the dose-expansion portion of the study in the UK, Spain, South Korea, USA and Australia with an expected 10 patients from the UK.

• REC name

  South Central - Berkshire Research Ethics Committee

• REC reference

  18/SC/0428

• Date of REC Opinion

  3 Oct 2018

• REC opinion

  Further Information Favourable Opinion