Clinical trial NCT01381874: 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
Official title: 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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic ER+ Her2- Breast Cancer
Postmenopausal
Keywords: Breast cancer
Abiraterone
Postmenopausal
Metastatic
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2011-06-27
Enrollment: 297
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Approximately 2 years
measure: Overall Survival (OS)
timeFrame: Approximately 3 years
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Approximately 2 years
measure: Clinical Benefit Rate
timeFrame: Approximately 2 years
measure: Duration of Response
timeFrame: Approximately 2 years
measure: Change From Baseline in Serum Endocrine Biomarkers (Estradiol and Estrone) at End of Treatment
timeFrame: Baseline and End of treatment (approximately 2 years)
measure: Change From Baseline in Serum Endocrine Biomarkers (Progesterone and Testosterone) at End of Treatment
timeFrame: Baseline and End of treatment (approximately 2 years)
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
state: Alabama
city: Fresno
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Monterey
country: United States
state: California
city: Chicago
country: United States
state: Illinois
city: Waterville
country: United States
state: Maine
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Henderson
country: United States
state: Nevada
city: East Syracuse
country: United States
state: New York
city: Johnson City
country: United States
state: New York
city: New York
country: United States
state: New York
city: Durham
country: United States
state: North Carolina
city: Fargo
country: United States
state: North Dakota
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Kettering
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Sioux Falls
country: United States
state: South Dakota
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Tyler
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Antwerpen
country: Belgium
city: Brussels
country: Belgium
city: Brussel
country: Belgium
city: Bruxelles
country: Belgium
city: Duffel
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Hasselt
country: Belgium
city: Leuven
country: Belgium
city: Liège
country: Belgium
city: Wilrijk
country: Belgium
city: Bordeaux
country: France
city: Caen Cedex 05
country: France
city: Pierre Benite
country: France
city: Saint Herblain
country: France
city: Saint-cloud
country: France
city: Galway
country: Ireland
city: Limerick
country: Ireland
city: Busan
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Suwon
country: Korea, Republic of
city: Luxembourg
country: Luxembourg
city: Niederkorn
country: Luxembourg
city: Alkmaar
country: Netherlands
city: Amsterdam
country: Netherlands
city: Heerlen
country: Netherlands
city: Leeuwarden
country: Netherlands
city: Leiden
country: Netherlands
city: Rotterdam
country: Netherlands
city: Sittard
country: Netherlands
city: Bialystok
country: Poland
city: Warszawa
country: Poland
city: Chelyabinsk
country: Russian Federation
city: Kazan
country: Russian Federation
city: Leningrad Region
country: Russian Federation
city: Moscow
country: Russian Federation
city: Saint-Petersburg,
country: Russian Federation
city: Sochi
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Stavropol
country: Russian Federation
city: Vladimir
country: Russian Federation
city: Barcelona
country: Spain
city: Madrid N/a
country: Spain
city: Madrid
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Chernivtsi
country: Ukraine
city: Dnepropetrovsk
country: Ukraine
city: Donetsk
country: Ukraine
city: Kharkov
country: Ukraine
city: Odessa
country: Ukraine
city: Tcherkassy
country: Ukraine
city: Uzhgorod
country: Ukraine
city: Bath
country: United Kingdom
city: Birmingham
country: United Kingdom
city: Exeter
country: United Kingdom
city: London
country: United Kingdom
city: Nottingham
country: United Kingdom
city: Plymouth
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Sutton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.