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An expanded access study for postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer who have progressed following prior endocrine therapy, investigating the treatment of everolimus (RAD001) in combination with exemestane

Conditions
Estrogen receptor positive locally advanced or metastatic breast cancer in postmenopausal women
MedDRA version: 14.1Level: LLTClassification code 10070575Term: Estrogen receptor positive breast cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2012-000073-23-AT
Lead Sponsor
ovartis Pharma Services AG
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Female
Target Recruitment
2200
Inclusion Criteria

1. Adult women (= 18 years of age) with metastatic or locally advanced breast cancer not amenable to curative treatment by surgery or radiotherapy, whose disease recurred or progressed following a NSAI treatment.
Letrozole or anastrozole do not have to be last treatment prior to study enrollment.
2. Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer and/or progesterone receptor-positive (PgR+)
3. Postmenopausal women. Postmenopausal status is defined either by:
•Age = 55 years and one year or more of amenorrhea
•Age < 55 years and one year or more of amenorrhea, with an estradiol assay < 20 pg/ml
•Surgical menopause with bilateral oophorectomy
4. Adequate bone marrow and coagulation function as shown by:
•Absolute neutrophil count (ANC) = 1.5 109/L
•Platelets = 100 ×109/L
•Hemoglobin (Hgb) = 9.0 g/dL
•INR = 2
5. Adequate liver function as shown by:
•Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 ULN (or = 5 if hepatic metastases are present)
•Total serum bilirubin = 1.5 × ULN (= 3 × ULN for patients known to have Gilbert Syndrome)
6. Adequate renal function as shown by:
•Serum creatinine = 1.5 × ULN
7. Fasting serum cholesterol = 300 mg/dl or 7.75 mmol/L and fasting triglycerides = 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy or other lipid lowering drugs (eg fibrates), and when the above mentioned values have been achieved
8. Written informed consent obtained before any screening procedure and according to local guidelines

Other protocol defined inclusion criteria may apply
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 500
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1700

Exclusion Criteria

1. HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ hybridization positive).
2. Pre-menopausal, pregnant, lactating women
3. Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin) or to their excipients.
4. Known hypersensitivity to exemestane, to the active substance or to any of the excipients.
5. Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose galactose malabsorption.
6. Radiotherapy within four weeks prior to enrollment except in case of localized radiotherapy for analgesic purpose or for lytic lesions at risk of fracture which can then be completed within two weeks prior to enrollment. Patients must have recovered from radiotherapy toxicities prior to enrollment.
7. Currently receiving hormone replacement therapy, unless discontinued prior to enrollment.
8. Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
Prolonged systemic corticosteroid treatment during study, except for topical applications (e.g. rash),inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intraarticular) should not be given. However, during the study:
•short duration (<2 weeks) of systemic corticosteroids is allowed (e.g. chronic obstructive pulmonary disease, anti-emetic) ;
•low doses of corticosteroids for brain metastasis treatment is allowed
9. Patients with symptomatic visceral disease in need of urgent disease control
10. Symptomatic brain or other CNS metastases.
Previously treated symptomatic brain metastases are allowed provided the patient is free of symptoms, prior radiotherapy for brain metastasis was more than four weeks before enrollment and the dose of corticosteroids is low and stable for at least two weeks prior to enrollment

Other protocol defined exclusion criteria may apply

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Timepoint(s) of evaluation of this end point: Adverse events: continuously, up to 28 days after last treatment<br>Laboratory values: continuously or as frequently as clinically indicated;Main Objective: to evaluate safety of everolimus (RAD001) in postmenopausal women with hormone receptor positive locally advanced or metastatic breast cancer after recurrence or progression following NSAIs treatment;Secondary Objective: - to evaluate adverse events grade 3 and 4 in the routine practice<br>- to explore the tolerability of the concomitant treatment of zoledronic acid RTU (Ready To Use) formulation in patients who will receive this treatment according to the clinical practice;Primary end point(s): frequency of adverse events and number of laboratory values that are new or worsening
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): - frequency of adverse events that is recorded as Grade 3 or 4 or as Serious Adverse Event <br>- 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 ;Timepoint(s) of evaluation of this end point: Continuously, up to 28 days after the last treatment
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