Studieoverzicht - 2012-01 BALLET

This will be a European, multi-center, open-label, single arm, phase III b study designed to make everolimus (RAD001) available to postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer refractory to NSAIs. Everolimus (RAD001) will be provided until the drug is locally reimbursed for this indication or until 31 January 2014, whichever comes first.

SCREENING PHASE

↓  Day -21 to  Day-1 ↓

TREATMENT PHASE

Everolimus (RAD001) 10 mg/day  +   Exemestane 25 mg/day

until

disease progression or unacceptable toxicity or death

or discontinuation from the study for any other reason

The primary objective of the study is to evaluate safety of everolimus (RAD001) in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer that is refractory to non steroidal aromatase inhibitors (NSAIs).

Primary endpoint

Frequency of adverse events and the number of laboratory values (hematology / chemistry) that are new or worsening based on the Common Terminology Criteria (CTCAE), version 4.03

Key secondary endpoint

The frequency of adverse events recorded as Grade 3 or 4 or as Serious Adverse Event. Adverse Event will be assessed by the Common Terminology Criteria (CTCAE), version 4.03.

Secondary exploratory endpoint

The frequency of adverse events of any grade in the group of patients who have received concomitant treatment with zoledronic acid RTU formulation, administered according to clinical practice Adverse event will be assessed by the Common Terminology Criteria (CTCAE), version 4.03.

Main inclusion criteria:

• Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy.
• Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
• Postmenopausal women.
  Note: Ovarian radiation or treatment with a luteinizing hormone-releasing hormone (LH-RH) agonist (goserelin acetate or leuprolide acetate) is not permitted for induction of ovarian suppression.
• Disease refractory to non steroidal aromatase inhibitors (NSAI), defined as:
  • Recurrence while on or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or
  • Progression while on or within one month of end of letrozole or anastrozole treatment for  advanced BC.

       Note: Letrozole or anastrozole do not have to be the last treatment prior to enrollment. Other prior anticancer therapy, e.g. tamoxifen, fulvestrant are allowed.

• Adequate bone marrow, coagulation, liver and renal functions; fasting cholesterol <7.75 mmol/L.

Main exclusion criteria:

• HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
• Previous treatment with exemestane or mTOR inhibitors. Except for the treatment with exemestane in the adjuvant setting providing patient remained disease-free for at least one year following completion.