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: 7 October 2014
• Main ID: EUCTR2012-000073-23-FI
• Date of registration: 23/07/2012
• 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: 03/09/2012
• Target sample size: 2200
• 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.
2.Histological or cytological confirmation of estrogen-receptor positive (ER+) breast cancer
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
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.
4.Disease refractory to NSAI, defined as:
a. Recurrence while on or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or
b. Progression while on or within one month of end of letrozole or anastrozole treatment for advanced BC
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
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.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.
3.Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).
4.Patients receiving concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry except in cases outlined below:
Topical applications, inhaled sprays, eye drops or local injections are allowed.
Patients on stable low dose of corticosteroids for at least two weeks before enrollment are allowed in case of treatment of brain metastases .
5.Bilateral diffuse lymphangitic carcinomatosis or metastasis of the lung as the only manifestation of disease (>50% of lung involvement), evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan.
6.Patients with a known history of HIV seropositivity.
7.Active, bleeding diathesis, or on oral anti-vitamin K medication (except low dose warfarin and acetylsalicylic acid or equivalent, as long as the INR is = 2.0)
8.Any severe and / or uncontrolled medical conditions such as:
•Uncontrolled diabetes as defined by fasting serum glucose > 1.5 × ULN
•Acute and chronic, active infectious disorders and nonmalignant medical illnesses that are uncontrolled or whose control may be jeopardized by the complications of this study therapy
•Significant symptomatic deterioration of lung function. If clinically indicated, pulmonary function tests including measures of predicted lung volumes, DLco, O2 saturation at rest on room air should be considered to exclude restrictive pulmonary disease, pneumonitis or pulmonary infiltrates.
9.Patients who test positive for hepatitis B or C (Patients who test negative for HBV-DNA, HBsAg, and HBcAb but positive for HBsAb with prior history of vaccination against Hepatitis B will be eligible)


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

Health Condition(s) or Problem(s) studied

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: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

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-

Primary Outcome(s)

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

Main Objective: to evaluate safety of everolimus (RAD001) in postmenopausal women with estrogen receptor positive locally advanced or metastatic breast cancer that is refractory to NSAIs

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)

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

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

Secondary ID(s)

2012-000073-23-AT

CRAD001YIC04

Source(s) of Monetary Support

Novartis Pharma Services AG