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

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

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.

Study Overview

• Status: Completed
• Conditions: Postmenopausal; Metastatic ER+ Her2- Breast Cancer
• Intervention / Treatment: Drug: Abiraterone acetate + Prednisone or Prednisolone; Drug: Abiraterone acetate + Prednisone/ Prednisolone + Exemestane; Drug: Exemestane

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 297
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium
  • Brussel, Belgium
  • Brussels, Belgium
  • Bruxelles, Belgium
  • Duffel, Belgium
  • Edegem, Belgium
  • Gent, Belgium
  • Hasselt, Belgium
  • Leuven, Belgium
  • Liège, Belgium
  • Wilrijk, Belgium
• France
  • Bordeaux, France
  • Caen Cedex 05, France
  • Pierre Benite, France
  • Saint Herblain, France
  • Saint-cloud, France
• Ireland
  • Galway, Ireland
  • Limerick, Ireland
• Korea, Republic of
  • Busan, Korea, Republic of
  • Seoul, Korea, Republic of
  • Suwon, Korea, Republic of
• Luxembourg
  • Luxembourg, Luxembourg
  • Niederkorn, Luxembourg
• Netherlands
  • Alkmaar, Netherlands
  • Amsterdam, Netherlands
  • Heerlen, Netherlands
  • Leeuwarden, Netherlands
  • Leiden, Netherlands
  • Rotterdam, Netherlands
  • Sittard, Netherlands
• Poland
  • Bialystok, Poland
  • Warszawa, Poland
• Russian Federation
  • Chelyabinsk, Russian Federation
  • Kazan, Russian Federation
  • Leningrad Region, Russian Federation
  • Moscow, Russian Federation
  • Saint-Petersburg,, Russian Federation
  • Sochi, Russian Federation
  • St Petersburg, Russian Federation
  • Stavropol, Russian Federation
  • Vladimir, Russian Federation
• Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Madrid N/a, Spain
  • Sevilla, Spain
  • Valencia, Spain
• Ukraine
  • Chernivtsi, Ukraine
  • Dnepropetrovsk, Ukraine
  • Donetsk, Ukraine
  • Kharkov, Ukraine
  • Odessa, Ukraine
  • Tcherkassy, Ukraine
  • Uzhgorod, Ukraine
• United Kingdom
  • Bath, United Kingdom
  • Birmingham, United Kingdom
  • Exeter, United Kingdom
  • London, United Kingdom
  • Nottingham, United Kingdom
  • Plymouth, United Kingdom
  • Sheffield, United Kingdom
  • Sutton, United Kingdom
• United States
  • Alabama
    • Muscle Shoals, Alabama, United States
  • California
    • Fresno, California, United States
    • Los Angeles, California, United States
    • Monterey, California, United States
  • Illinois
    • Chicago, Illinois, United States
  • Maine
    • Waterville, Maine, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Ann Arbor, Michigan, United States
  • Nevada
    • Henderson, Nevada, United States
  • New York
    • East Syracuse, New York, United States
    • Johnson City, New York, United States
    • New York, New York, United States
  • North Carolina
    • Durham, North Carolina, United States
  • North Dakota
    • Fargo, North Dakota, United States
  • Ohio
    • Cleveland, Ohio, United States
    • Columbus, Ohio, United States
    • Kettering, Ohio, United States
  • Oregon
    • Portland, Oregon, United States
  • South Dakota
    • Sioux Falls, South Dakota, United States
  • Texas
    • Dallas, Texas, United States
    • El Paso, Texas, United States
    • Houston, Texas, United States
    • Tyler, Texas, United States
  • Washington
    • Seattle, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• O'Shaughnessy J, Campone M, Brain E, Neven P, Hayes D, Bondarenko I, Griffin TW, Martin J, De Porre P, Kheoh T, Yu MK, Peng W, Johnston S. Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer. Ann Oncol. 2016 Jan;27(1):106-13. doi: 10.1093/annonc/mdv487. Epub 2015 Oct 26.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2011
• Primary Completion (Actual): July 28, 2014
• Study Completion (Actual): August 8, 2018

Study Registration Dates

• First Submitted: June 23, 2011
• First Submitted That Met QC Criteria: June 23, 2011
• First Posted (Estimate): June 27, 2011

Study Record Updates

• Last Update Posted (Actual): April 11, 2019
• Last Update Submitted That Met QC Criteria: March 28, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Breast cancer; Metastatic; Postmenopausal; Abiraterone
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Cytochrome P-450 Enzyme Inhibitors; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Prednisone; Abiraterone Acetate; Exemestane
• Other Study ID Numbers: CR018286; 212082BCA2001 (Other Identifier: Janssen Research & Development, LLC); 2011-000621-80 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No