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

NCT ID: NCT01381874

Last Updated: 2019-04-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 297 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-24
• Study Completion Date: 2018-08-08

Brief Summary

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

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.

Conditions

Metastatic ER+ Her2- Breast Cancer; Postmenopausal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Abiraterone acetate + Prednisone or Prednisolone

Intervention Type: DRUG

Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets

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.

Group Type: EXPERIMENTAL

Abiraterone acetate + Prednisone/ Prednisolone + Exemestane

Intervention Type: DRUG

Prednisone or Prednisolone, type=equal, unit=mg, number=5, form=tablet, route=oral use. All drugs are taken once daily.

Exemestane

Exemestane Exemestane type=equal unit=mg number=25 form=tablet route=oral use. All drugs are taken once daily.

Group Type: EXPERIMENTAL

Exemestane

Intervention Type: DRUG

Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets

Interventions

Exemestane

Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets

Intervention Type: 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.

Intervention Type: DRUG

Abiraterone acetate + Prednisone or Prednisolone

Abiraterone acetate, type=equal, unit=mg, number=250, form=tablet, route=oral use, 4 tablets

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Muscle Shoals, Alabama, United States

Fresno, California, United States

Los Angeles, California, United States

Monterey, California, United States

Chicago, Illinois, United States

Waterville, Maine, United States

Boston, Massachusetts, United States

Ann Arbor, Michigan, United States

Henderson, Nevada, United States

East Syracuse, New York, United States

Johnson City, New York, United States

New York, New York, United States

Durham, North Carolina, United States

Fargo, North Dakota, United States

Cleveland, Ohio, United States

Columbus, Ohio, United States

Kettering, Ohio, United States

Portland, Oregon, United States

Sioux Falls, South Dakota, United States

Dallas, Texas, United States

El Paso, Texas, United States

Houston, Texas, United States

Tyler, Texas, United States

Seattle, Washington, United States

Antwerp, , Belgium

Brussels, , Belgium

Duffel, , Belgium

Edegem, , Belgium

Ghent, , Belgium

Hasselt, , Belgium

Leuven, , Belgium

Liège, , Belgium

Wilrijk, , Belgium

Bordeaux, , France

Caen, , France

Pierre-Bénite, , France

Saint-Cloud, , France

Saint-Herblain, , France

Galway, , Ireland

Limerick, , Ireland

Luxembourg, , Luxembourg

Niedercorn, , Luxembourg

Alkmaar, , Netherlands

Amsterdam, , Netherlands

Heerlen, , Netherlands

Leeuwarden, , Netherlands

Leiden, , Netherlands

Rotterdam, , Netherlands

Sittard, , Netherlands

Bialystok, , Poland

Warsaw, , Poland

Chelyabinsk, , Russia

Kazan', , Russia

Leningrad Region, , Russia

Moscow, , Russia

Saint Petersburg, , Russia

Sochi, , Russia

Stavropol, , Russia

Vladimir, , Russia

Busan, , South Korea

Seoul, , South Korea

Suwon, , South Korea

Barcelona, , Spain

Madrid, , Spain

Seville, , Spain

Valencia, , Spain

Cherkasy, , Ukraine

Chernivtsi, , Ukraine

Dnipro, , Ukraine

Donetsk, , Ukraine

Kharkiv, , Ukraine

Odesa, , Ukraine

Uzhhorod, , Ukraine

Bath, , United Kingdom

Birmingham, , United Kingdom

Exeter, , United Kingdom

London, , United Kingdom

Nottingham, , United Kingdom

Plymouth, , United Kingdom

Sheffield, , United Kingdom

Sutton, , United Kingdom

Countries

United States; Belgium; France; Ireland; Luxembourg; Netherlands; Poland; Russia; South Korea; Spain; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26504153 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

212082BCA2001

Identifier Type: OTHER

Identifier Source: secondary_id

2011-000621-80

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR018286

Identifier Type: -

Identifier Source: org_study_id

NCT01355770

Identifier Type: -

Identifier Source: nct_alias