Randomized, Open-Label Study of Abiraterone Acetate (JNJ-212082) Plus Prednisone With or Without Exemestane in Postmenopausal Women With ER+ Metastatic Breast Cancer Progressing After Letrozole or Anastrozole Therapy.

Study Objective

Primary Objective

The primary objective is to assess the safety and efficacy of abiraterone acetate plus prednisone and abiraterone acetate plus prednisone combined with exemestane, each compared with Exemestane alone, in postmenopausal women with ER+ metastatic breast cancer progressing after letrozole or anastrozole therapy.

Secondary Objective(s)

To assess abiraterone acetate plus prednisone and abiraterone acetate plus prednisone combined with exemestane, each compared with exemestane alone, in postmenopausal women with ER+ metastatic breast cancer progressing after letrozole or anastrozole therapy, with respect to the following:
• Overall survival
• Overall response rate
• Patient-reported outcomes (PROs), EORTC-C30, EQ-5D-5L, and BPI-SF pain intensity scale
• Endocrine markers estradiol, testosterone, estrone, and other biomarkers
• Pharmacokinetics (PK) characterization of abiraterone and exemestane

Participation conditions

Inclusion Criteria

1. Woman ≥18 years of age and postmenopausal determined by one of the following:
• bilateral, surgical oophorectomy
• age ≥ 60 years
• age < 60 years, with amenorrhea ≥ 24 months and follicle-stimulating hormone and
luteinizing hormone concentrations within postmenopausal range

2. Subjects with ER+, Her2- metastatic breast cancer.
3. Subjects with disease confined only to bone may be included but subjects with purely sclerotic lesions may not participate in the study.
4. Disease must have been sensitive to anastrozole or letrozole therapy prior to disease progression.
5. No more than 2 prior lines of therapy in the metastatic setting, of which no more than 1 was
Chemotherapy.
6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1
7. Clinical laboratory values during Screening:
• hemoglobin ≥ 10.0 g/dL
• neutrophils ≥ 1.5 x 109/L
• platelets ≥ 100 x 109/L
• total bilirubin ≤ 1.5x upper limit of normal (ULN)
• alanine (ALT) and aspartate (AST) aminotransferase ≤ 2.5xULN
• alkaline phosphatase ≤ 6xULN unless bone metastases with no liver disorder
• serum creatinine < 1.5xULN or creatinine clearance ≥ 50 mL/min
• serum potassium ≥ 3.5 mM
• serum albumin ≥ 3.0 g/dL
• prothrombin time (PT) and partial thromboplastin time (PTT) within normal limits
8. Systolic blood pressure < 160 mm Hg and diastolic blood pressure <95 mm Hg
9. Cardiac ejection fraction ≥ 50% measured by MUGA or ECHO done within 4 weeks before
randomization.
10. A bisphosphonate or denosumab may be initiated on the same day as the assigned
study treatment
11. Willing and able to adhere to prohibitions and restrictions specified in this protocol
12. Signs an informed consent document

Exclusion Criteria

1. Prior treatment with exemestane, ketoconazole, aminoglutethimide or a CYP17 inhibitor.
2. Anticancer immunotherapy or investigational agent within 4 weeks before randomization, or anticancer radiotherapy (except palliative) or anticancer endocrine therapy within 2 weeks before randomization.
3. Serious or uncontrolled nonmalignant disease, including active or uncontrolled infection.
4. Clinical or biochemical evidence of hyperaldosteronism or hypopituitarism.
5. Any condition that, in the opinion of the investigator, would compromise the well-being of
the patient or that could prevent, limit, or confound the protocol-specified assessments.
6. Major thoracic or abdominal surgery or significant traumatic injury with 4 weeks before
randomization or plans surgery during study participation or within 4 weeks after the last
dose of study drug.
7. Persistent ≥ Grade 2 toxicity from any cause.
8. Symptomatic central nervous system disease or leptomeningeal disease.
9. Gastrointestinal disorder interfering with study drug absorption.
10. Active or uncontrolled disease that may require oral corticosteroid therapy.
11. Positive serology for hepatitis B surface antigen or hepatitis C antibody.
12. Active or symptomatic viral hepatitis or chronic liver disease.
13. History of clinically significant heart disease, ie, myocardial infarction or arterial thrombotic
event within 6 months, severe or unstable angina, or New York Heart Association Class III or IV heart disease
14. Known allergies, hypersensitivity, or intolerance to abiraterone acetate, exemestane, prednisone, or their excipients.
15. Contraindications to the use of exemestane or prednisone per local prescribing information.
16. Received an investigational drug (including investigational vaccines) or used an invasive
investigational medical device within 4 weeks before the planned first dose of study drug or
is currently enrolled in an investigational study
 

Centre Hospitalier de Luxembourg (CHL);

Centre Hospitalier Emile Mayrisch (CHEM)