A Study of Abiraterone Acetate Plus Prednisone With or Without Exemestane in Postmenopausal Women With Estrogen Receptor-Positive (ER+) Metastatic Breast Cancer Progressing After Letrozole or Anastrozole Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of oral abiraterone acetate plus oral prednisone and oral abiraterone acetate plus oral prednisone plus oral exemestane, each compared with oral exemestane alone, in postmenopausal women with estrogen receptor-positive (ER+) metastatic (spreading) breast cancer that has relapsed after treatment with letrozole or anastrozole.

Detailed Description
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This is a randomized (study drug assigned by chance), open-label (all participants will know the identity of the assigned study drug) study divided into three phases, screening, treatment, and follow-up. During screening, potential patients will be assessed for study eligibility after providing signed informed consent. The treatment phase will comprise a series of 28-day cycles with continuous study treatment until breast cancer progression, when an end-of-treatment visit will be completed before the follow-up phase begins. The duration of participation in the study for an individual patient may be up to approximately 7 years, including follow-up evaluations. Patients will be evaluated for the safety and effectiveness of study treatments. During the treatment phase, patients will take the following study drugs by mouth once daily: abiraterone acetate, 1 g/day, as four 250-mg tablets, on an empty stomach, and patients must not eat for at least 1 hour after abiraterone acetate; prednisone (prednisolone when prednisone is not available), 5 mg/day; and exemestane, 25 mg/day, as a single tablet. The treatment phase will consist of a series of 28-day cycles with continuous study treatment until breast cancer progression. At the planned interim analysis, the Data Review Committee has recommended that further randomization to the abiraterone acetate alone group be stopped and that the study is to be continued otherwise.

Official Title
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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

Conditions
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Metastatic ER+ Her2- Breast Cancer, Postmenopausal

Intervention / Treatment
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* Drug: Exemestane
* Drug: Abiraterone acetate + Prednisone/ Prednisolone + Exemestane
* Drug: Abiraterone acetate + Prednisone or Prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female patients must be postmenopausal ER+, Human epidermal growth factor receptor 2 (Her2) negative metastatic breast cancer Disease must have been sensitive to anastrozole or letrozole therapy prior to disease progression No more than two prior lines of therapy in the metastatic setting, of which no more than one was chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status score of <=1 Patients with disease confined only to bone may be included, but patients with purely sclerotic lesions may not participate in the study Exclusion Criteria: Prior treatment with exemestane, ketoconazole, aminoglutethimide, or a CYP17 inhibitor. Prior treatment with ketoconazole for <= 7 days is permitted and topical formulations of ketoconazole are permitted Potential patients must not have taken anastrozole, letrozole, fulvestrant, or any chemotherapy for at least 2 weeks (bevacizumab for at least 3 weeks) before randomization Anticancer immunotherapy or investigational agent within 4 weeks before randomization, or anticancer radiotherapy (except palliative) or anticancer endocrine therapy within 2 weeks before randomization Serious or uncontrolled nonmalignant disease, including active or uncontrolled infection Clinical or biochemical evidence of hyperaldosteronism or hypopituitarism 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abiraterone acetate + Prednisone or Prednisolone<br>Abiraterone acetate + Prednisone or Prednisolone Abiraterone acetate type=equal unit=mg number=250 form=tablet route=oral use 4 tablets Prednisone or Prednisolone type=equal unit=mg number=5 form=tablet route=oral use. All drugs are taken once daily. | Drug: Abiraterone acetate + Prednisone or Prednisolone<br>* Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets<br>|
| Experimental: Abiraterone acetate + Prednisone/Prednisolone + Exemestane<br>Abiraterone acetate + Prednisone/Prednisolone + Exemestane Abiraterone acetate type=equal unit=mg number=250 form=tablet route=oral use 4 tablets Prednisone or Prednisolone type=equal unit=mg number=5 form=tablet route=oral use Exemestane type=equal unit=mg number=25 form=tablet route=oral use. All drugs are taken once daily. | Drug: Abiraterone acetate + Prednisone/ Prednisolone + Exemestane<br>* Prednisone or Prednisolone, type=equal, unit=mg, number=5, form=tablet, route=oral use. All drugs are taken once daily.<br>|
| Experimental: Exemestane<br>Exemestane Exemestane type=equal unit=mg number=25 form=tablet route=oral use. All drugs are taken once daily. | Drug: Exemestane<br>* Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Progression-free survival was defined as the time from randomization to first occurrence of disease progression (either radiographic or clinical), or death from any cause. PFS was determined using radiographic progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) on measurable lesions captured by computed tomography (CT) or magnetic resonance imaging (MRI). Clinical disease progression was considered only when disease progression could not be confirmed by CT or MRI, such as when the disease site is skin, bone marrow, or central nervous system. | Approximately 2 years | 
| Overall Survival (OS) | OS was calculated as the time from randomization to death from any cause. | Approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | Overall response rate was defined as the percentage of participants with measurable disease achieving a best overall response of either complete response (CR) or partial response (PR) based on RECIST. CR: disappearance of all target lesions and non-target lesions. PR: at least a 30 percent (%) decrease in the sum of longest diameter (LD) of target lesions or persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits. | Approximately 2 years | 
| Clinical Benefit Rate | Clinical benefit rate was defined as the percentage of participants with measurable disease achieving a best overall response of a CR, PR, or stable disease (SD) for at least 6 months based on RECIST. Stable disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study and persistence of one or more non-target lesion(s) and/or maintenance of tumour marker level above the normal limits. | Approximately 2 years | 
| Duration of Response | Duration of objective response was measured from the first time that the CR or PR was achieved to the first observation of disease progression (either radiographic or clinical) based on the RECIST criteria. | Approximately 2 years | 
| Change From Baseline in Serum Endocrine Biomarkers (Estradiol and Estrone) at End of Treatment | Change from baseline in serum endocrine biomarkers (estradiol and estrone) was summarized by treatment at end of treatment. | Baseline and End of treatment (approximately 2 years) | 
| Change From Baseline in Serum Endocrine Biomarkers (Progesterone and Testosterone) at End of Treatment | Change from baseline in serum endocrine biomarkers (Progesterone and Testosterone) was summarized by treatment at end of treatment. | Baseline and End of treatment (approximately 2 years) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Breast cancer, Abiraterone, Postmenopausal, Metastatic