A Randomized Double-Blind, Placebo-Controlled Study of Everolimus in Combination with Exemestane in the Treatment of Postmenopausal Women with Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer who are refractory to Letrozole or Anastrozole.

• Conditions: Estrogen Receptor Positive Locally Advanced or Metastatic Breast Cancer; MedDRA version: 9.1Level: LLTClassification code 10006187Term: Breast cancer

• Registration Number: EUCTR2008-008698-69-HU
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-09-01
• Last Update Posted: 2 February 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Female
• Target Recruitment: 705

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. 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.

? 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 ABC.

? Radiological or clinical evidence of recurrence or progression on last systemic
therapy prior to randomization.

? Patients must have:
? At least one lesion that can be accurately measured in at least one dimension =
20 mm with conventional imaging techniques or = 10 mm with spiral CT or MRI or
? bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable
disease as defined above.

? Adequate bone marrow and coagulation function as shown by:
? Absolute neutrophil count (ANC) = 1.5x10 9/L
? Platelets = 100 ×10 9/L
? Hemoglobin (Hgb) = 9.0 g/dL
? INR = 2

? 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 x ULN for patients known to have Gilbert Syndrome)

? Adequate renal function as shown by:
? Serum creatinine = 1.5 × ULN

? 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 and when the above mentioned
values have been achieved

? ECOG Performance Status = 2

? Written informed consent obtained before any screening procedure and according to local guidelines.

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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

? HER2-overexpressing patients by local laboratory testing (IHC 3+ staining or in situ
hybridization positive).

? Patients with only non-measurable lesions other than bone metastasis (e.g. pleural
effusion, ascites etc.).

? Patients who received more than one chemotherapy regimen for ABC.

? Previous treatment with exemestane or mTOR inhibitors.

? Known hypersensitivity to mTOR inhibitors, e.g. sirolimus (rapamycin).

? Another malignancy within 5 years prior to randomization, with the exception of
adequately treated in-situ carcinoma of the cervix, uteri, basal or squamous cell
carcinoma or non-melanomatous skin cancer.

? Radiotherapy within four weeks prior to randomization 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 randomization. Patients must have
recovered from radiotherapy toxicities prior to randomization.

? Currently receiving hormone replacement therapy, unless discontinued prior to
randomization.

? Symptomatic brain or other CNS metastases
Previously treated brain metastases are allowed provided the patient is free of
symptoms, prior radiotherapy for brain metastasis was more than four weeks
before randomization and the dose of corticosteroids is stable for at least two
weeks prior to randomization.

• 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 randomization are allowed in case of previously treated brain metastases.

? 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.

? Patients with a known history of HIV seropositivity. Screening for HIV infection at
baseline is not required.

? 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)

? Any severe and / or uncontrolled medical conditions such as:
? Unstable angina pectoris, symptomatic congestive heart failure, myocardial
infarction =6 months prior to enrollment, serious uncontrolled cardiac arrhythmia
? 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
? Impairment of gastrointestinal function or who have gastrointestinal disease that
may significantly alter the absorption of study drugs (e.g., ulcerative disease,
uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome)
? Active skin, mucosa, ocular or GI disorders of Grade > 1
? 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.

? Patients being treated with drugs recognized as being strong inhibitor

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified