Estrogen Receptor Positive Breast Cancer

• Research type

  Research Study

• Full title

  A Phase 1b/2 Study of GS-5829 in Combination with Fulvestrant or Exemestane in Subjects with Advanced Estrogen Receptor Positive, HER2 Negative-Breast Cancer

• IRAS ID

  218473

• Contact name

  Stephen Johnston

• Contact email

  stephen.johnston@rmh.nhs.uk

• Sponsor organisation

  Gilead Sciences Inc

• Eudract number

  2016-002365-63

• Clinicaltrials.gov Identifier

  NCT02983604

• Duration of Study in the UK

  3 years, 3 months, 1 days

• Research summary

  This study targets patients who have Avanced Estrogen Receptor Positive HER2- Breast Cancer. Approximately 75% of breast cancers express the estrogen receptor (ER), a nuclear hormone receptor and transcription factor that promotes the expression of genes involved in cell growth and survival. Anti-estrogen endocrine therapies, such as aromatase inhibitors (AIs) and tamoxifen, are the primary treatments for early stage ER-positive breast cancers but many women relapse during or after completing these adjuvant hormonal therapies. In the metastatic setting, single-agent treatment with AIs, tamoxifen, or the selective ER degrader, fulvestrant, has limited benefit. When combined with other targeted therapies such as the Cyclin-Dependent Kinase (CDK) 4/6 inhibitor, palbociclib, the benefit of first-line antiestrogen therapy significantly improves progression free survival. Standard of care includes sequential administration of endocrine therapies until hormone resistance occurs, at which time patients are usually transitioned to chemotherapy and eventually die.
  Gilead is conducting this 2 part study to evaluate the efficacy, safety and tolerability of GS-5829 (study drug) which is under development for the treatment of breast cancer. GS-5829 is currently being evaluated in 2 ongoing studies in subjects with advanced solid tumours, ER+Her2- breast cancer, and lymphomas and prostate cancer. The Phase 1b study will be conducted in the USA and Phase 2 study will be conducted in Europe only.
  For information only- Phase 1b dose escalation is the first part of this study enrolling participants into cohorts at progressively higher dose levels of GS-5829 in combination with exemstane or fulverstrant to determine the maximum tolerated dose (MTD).
  The MTD of GS-5829 will be used in the Randomized Phase 2 dose expansion study combined with exemestane compared with exemestane alone or GS-5829 combined with fulverstrant compared with fulverstrant alone.
  180 participants (120 in phase 2 study) will participate from across sites in 6 countries. Participants will be required to visit the clinic on Day 1 and return on Day 15 of the first and second cycles. For cycle 3 participants will be required to visit the clinic on Day 1 and return once every 4 weeks thereafter. Each cycle is 28 days long. If or when participants stop treatment on this study an in clinic Safety Follow-up Visit 30 days after the last dose of any of the study drugs will be done.
  If participants decide to stop taking the study treatment they can participate in a a Long-Term Survival Follow-up period which lasts for up to two years from the date study medication is stopped.
  Participants may continue receiving GS-5829 once daily until disease progression (clinical or radiographic), unacceptable toxicity, withdrawal of consent or death, whichever comes first

• REC name

  South Central - Berkshire Research Ethics Committee

• REC reference

  17/SC/0130

• Date of REC Opinion

  27 Mar 2017

• REC opinion

  Favourable Opinion