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

• Register: EUCTR
• Last refreshed on: 17 August 2015
• Main ID: EUCTR2012-000073-23-BE
• Date of registration: 24/07/2012
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: 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
• Scientific title: An open-label, multi-center, 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
• Date of first enrolment: 17/09/2012
• Target sample size: 1600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-000073-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1

Countries of recruitment

Austria, Belgium, Bulgaria, Denmark, Finland, Hungary, Ireland, Italy, Netherlands, Norway, Slovakia, Spain, Sweden

Key inclusion & exclusion criteria

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. Radiological or clinical evidence of recurrence or progression on last therapy prior to enrollment.
5. 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
6. 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)
7. Adequate renal function as shown by:
• Serum creatinine = 1.5 × ULN
8. 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
9. 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 360
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1240

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 (baseline/treatment start) 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 (baseline/treatment start). 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Estrogen receptor positive locally advanced or metastatic breast cancer in postmenopausal women
MedDRA version: 14.1 Level: LLT Classification code 10070575 Term: Estrogen receptor positive breast cancer System Organ Class: 100000004864

Intervention(s)

Trade Name: Afinitor
Product Name: Everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Trade Name: Afinitor
Product Name: Everolimus
Product Code: RAD001
Pharmaceutical Form: Tablet
INN or Proposed INN: everolimus
CAS Number: 159351-69-6
Current Sponsor code: RAD001
Other descriptive name: EVEROLIMUS
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10-

Product Name: exemestane
Pharmaceutical Form: Coated tablet
INN or Proposed INN: exemestane
CAS Number: 107868-30-4
Other descriptive name: EXEMESTANE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Caphosol
Product Name: Caphosol
Pharmaceutical Form: Mouthwash

Primary Outcome(s)

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

Primary end point(s): frequency of adverse events and number of laboratory values that are new or worsening

Secondary Objective: - to evaluate adverse events grade 3 and 4 in the routine practice
- 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

Timepoint(s) of evaluation of this end point: Adverse events: continuously, up to 28 days after last treatment
Laboratory values: continuously or as frequently as clinically indicated

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Continuously, up to 28 days after the last treatment

Secondary end point(s): - frequency of adverse events that is recorded as Grade 3 or 4 or as Serious Adverse Event
- 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

Secondary ID(s)

CRAD001YIC04

2012-000073-23-AT

Source(s) of Monetary Support

Novartis Pharma Services AG