Fulvestrant and Ipatasertib for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor

• Status: Recruiting
• Trial end date: 2026-12-31
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to find out whether a new drug, Ipatasertib, can slow the growth of advanced breast cancer when added to standard therapy (Fulvestrant).

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Canadian Cancer Trials Group
• Collaborator: Hoffmann-La Roche
• Treatments: Fulvestrant

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• Untreated or symptomatic CNS metastases, radiation treatment for CNS metastases within 28 days

• Active inflammatory bowel disease, bowel inflammation, inability to swallow oral medication or GI condition that alters oral absorption

• Prior treatment with fulvestrant, selective estrogen receptor degraders (SERDs) or known inhibitors of the PI3K pathway including PI3K inhibitors, AKT inhibitors, or mTOR inhibitors

• Mean QT interval corrected for heart rate (QTc) ≥ 480 msec by ECG or history of familial long QT syndrome

• Active or uncontrolled infections or serious illnesses or medical conditions

• Clinically significant liver diseases

• History of lung disease or history of opportunistic infections

• Type 1 or Type 2 diabetes mellitus requiring insulin

• Grade ≥ 2 uncontrolled hypercholesterolemia or hypertriglyceridemia

• Known abnormalities in coagulation

• History of hypersensitivity to the study drugs or components

• Pregnant or lactating women