FINER: This phase III trial is trying to find out if a new targeted therapy (Ipatasertib) can slow the growth of advanced breast cancer when added to standard hormone therapy (Fulvestrant)A Double-Blind Placebo-Controlled Randomized Phase III Trial of Fulvestrant and Ipatasertib as Treatment for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor

Inclusion

• Histologically and/or cytologically confirmed ER positive, HER-2 negative breast cancer
• Female patients must be post-menopausal; female patients who are pre-menopausal must have ovarian suppression using LHRH agonist while on study
• Clinical and/or radiographic progression during treatment with or within 28 days after discontinuation of first line of treatment with a CDK 4/6 inhibitor and an aromatase inhibitor (AI) for advanced/metastatic disease
• Evidence of clinically and/or radiologically documented disease
• ≥ 18 years of age
• ECOG performance status of 0 or 1

• No concurrent anti-cancer therapy and must satisfy the following criteria for previous therapy

  • Must not have received more than one prior line of treatment with a CDK 4/6 inhibitor and an AI in the advanced disease setting.
  • Treatment with CDK 4/6 inhibitor and AI must have been the most recent treatment prior to registration for this study

• Adequate hematology and organ function, in the absence of growth factors

  • Absolute neutrophils > 1.5 x 10^9/L
  • Platelets ≥ 100 x 10^9/L
  • Hemoglobin > 90 g/L
  • Total Bilirubin ≤ 1.5 x ULN (upper limit of normal) or ≤ 3 x ULN if confirmed Gilbert's Syndrome
  • ALT and AST ≤ 2.5 x ULN (or ≤ 5.0 x ULN if liver or bone metastasis)
  • Alkaline phosphatase ≤ 2.0 x ULN (or ≤ 5.0 x ULN if liver metastases, ≤ 7.0 x ULN if bone metastasis)
  • Fasting glucose ≤ 8.3 mmol/L
  • HbA1c ≤ 7.5%
  • Serum albumin ≥ 30 g/L
  • INR ≤ 1.2
  • Serum Creatinine or Creatinine clearance ≤ 1.5 x ULN or ≥ 50 mL/min; measured directly by 24-hour urine sampling or as calculated by Crockcroft and Gault equation