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 (FINER)

Canadian Cancer Trials Group

Status and phase

Active, not recruiting

Phase 3

Conditions

Breast Cancer

Treatments

Drug: Ipatasertib

Other: Placebo

Drug: Fulvestrant

Study type

Interventional

Funder types

NETWORK

Industry

Identifiers

NCT04650581

M041883 (Other Identifier)

MA40

2101

Details and patient eligibility

About

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).

Full description

Patients enrolled in this study will receive either Ipatasertib plus Fulvestrant or placebo (a substance that looks like the study drug but does not have any active or medicinal ingredient) plus Fulvestant. The study will provide information about the ability of Ipatasertib plus Fulvestrant to control the cancer, the side effects and safety of the treatment, how patients feel while taking the treatment and associated costs.

Enrollment

250 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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