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

• Register: EUCTR
• Last refreshed on: 26 January 2015
• Main ID: EUCTR2011-000621-80-IE
• Date of registration: 09/08/2012
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: 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
• Scientific 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
• Date of first enrolment: 15/10/2012
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-000621-80
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Belgium, France, Ireland, Italy, Korea, Republic of, Luxembourg, Netherlands, Poland, Russian Federation, Spain, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

• Name: Clinical Registry Group
• Affiliation: Janssen-Cilag International NV

Key inclusion & exclusion criteria

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, confirmed within 7 days before randomization with FFPE tissue from either primary or metastatic breast cancer site. In a subject with multiple biopsies of metastatic sites, the most recent biopsy prior to study entry should be submitted for evaluation of hormone receptor status.
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. Sensitivity to anastrozole or letrozole is defined as either stable disease or better for >=6 months in the metastatic setting or relapse free for >=2 years in the adjuvant setting.
5. No more than two prior lines of therapy in the metastatic setting, of which no more than one was chemotherapy [Note: Simultaneous combination treatment is considered one line of therapy.]
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 10^9/L
•platelets >=100 x 10^9/L
Note: Subjects need to meet the above 3 criteria independent of growth factors and transfusions
•total bilirubin <=1.5 x 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 [Exception: PT and international normalized ratio (INR) will be abnormally prolonged in subjects taking warfarin.]
8. Systolic blood pressure <160 mm Hg and diastolic blood pressure <95 mm Hg [Note: Hypertension controlled by antihypertensive therapy is permitted].
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.
11 Willing and able to adhere to prohibitions and restrictions specified in this protocol
12 Signs an informed consent document within 4 weeks before randomization indicating she understands the purpose of and procedures required for the study and is willing to participate in the study
13 Signs the informed consent document within 4 weeks before randomization for pharmacogenomics research indicating willingness to participate in the pharmacogenomic component of the study, where local regulations permit. [Note: Refusal to give consent for this component does not exclude a subject from participation in this clinical study.]
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion criteria:
1. Prior treatment with exemestane, ketoconazole, aminoglutethimide, or a CYP17 inhibitor [Note: Prior treatment with ketoconazole for <= 7 days is permitted and topical formulations of ketoconazole are permitted]
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 [Note: Potential subjects must not have taken anastrozole, letrozole, fulvestrant, or any chemotherapy for at least 2 weeks (bevacizumab for at least 3 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 [Note: Patients with planned surgical procedures to be conducted under local anesthesia are not excluded from the study.]
7. Persistent >=Grade 2 toxicity from any cause [Note: Chemotherapy-induced alopecia and Grade 2 peripheral neuropathy are allowed.]
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. Active or symptomatic viral hepatitis or chronic liver disease
12. 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
13. Known allergies, hypersensitivity, or intolerance to abiraterone acetate, exemestane, prednisone, or their excipients
14. Contraindications to the use of exemestane or prednisone per local prescribing information
15. 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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Metastatic Breast Cancer
MedDRA version: 14.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: ZYTIGA
Product Name: Abiraterone acetate
Product Code: JNJ-212082
Pharmaceutical Form: Tablet
INN or Proposed INN: Abiraterone acetate
CAS Number: 154229-18-2
Current Sponsor code: CB7630
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 250-

Product Name: Prednisolone
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
CAS Number: 50-24-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: exemestane
Pharmaceutical Form: Coated tablet
INN or Proposed INN: EXEMESTANE
CAS Number: 107868-30-4
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Primary end point(s): Progression free survival

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

Secondary Objective: Secondary objectives are 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
•PK characterization of abiraterone and exemestane

Timepoint(s) of evaluation of this end point: Up to approximately 1.5 years

Secondary Outcome(s)

Secondary end point(s): 1. Overall survival
2. Overall response rate to treatment
3. Patient-reported outcomes
4. Pharmacodynamics
5. Pharmacokinetics

Timepoint(s) of evaluation of this end point: 1. Up to approximately 3.5 years
2. Up to 1.5 years
3. Up to approximately 3.5 years
4. Up to approximately 1.5 years
5. Approximately 4 months

Secondary ID(s)

212082BCA2001

2011-000621-80-BE

Source(s) of Monetary Support

Janssen Research & Development