Clinical trial NCT01814865: Anti-Proliferative Effects and Genomic Alterations of Abiraterone Acetate Compared to an Aromatase Inhibitor in Post-menopausal HR+ Operable Breast Cancer
Official title: Pre-operative Assessment of the Anti-Proliferative Effects and Genomic Alterations of 2 Weeks of Abiraterone Acetate Compared to 2 Weeks of an Aromatase Inhibitor in Post-menopausal Hormone Receptor Positive Operable Breast Cancer
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Post-menopausal ER+ Stage I-IIIA Primary Operable Breast Cancer
Keywords: Post-menopausal
ER+
Stage I-IIIA
Operable
Breast Cancer
Lead sponsor: British Columbia Cancer Agency
Sponsor class: OTHER
Collaborators: name: Janssen Research & Development, LLC
First posted: 2013-03-20
Enrollment: 0
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This study is being offered to patients who are post-menopausal, have breast cancer with a positive estrogen and/or progesterone hormone receptor test and are currently awaiting surgery for breast cancer.

The purpose of this study is to determine whether abiraterone acetate has different hormonal and genomic effects than non-steroidal aromatase inhibitors in the treatment of post-menopausal hormonal receptor positive primary operable breast cancer


Eligibility criteria: Inclusion Criteria:

1. Woman greater than or equal to 18 years of age and postmenopausal determined by one of the following:

   * bilateral surgical oophorectomy
   * age greater than or equal 60 years
   * age \<60 years, with amenorrhea greater than or equal 24 months and follicle-stimulating hormone and luteinizing hormone concentrations within postmenopausal range
2. Subjects with ER+ (Allred 3-8), HER2 - primary operable T1-T3 breast cancer with a primary tumor size of ≥ 1.5 cm on physical examination or imaging studies
3. Eastern Cooperative Oncology Group (ECOG) performance status score of less than or equal to 1
4. Criterion modified per amendment 7.1 Clinical laboratory values during Screening:

   * hemoglobin greater than or equal 10.0 g/dL
   * neutrophils greater than or equal 1.5 x 109/L
   * platelets greater than or equal100 x 109/L
   * total bilirubin less than or equal to 1.5x upper limit of normal (ULN) - except for a known diagnosis of Gilbert's syndrome
   * alanine (ALT) and aspartate (AST) aminotransferase less than or equal to 1.5xULN
   * alkaline phosphatase less than or equal to 1.5xULN
   * serum creatinine \<1.5xULN or creatinine clearance greater than or equal 45 mL/min
   * serum potassium greater than or equal 3.5 mM
   * serum albumin greater than or equal 3.0 g/dL
   * INR (or PT) and partial thromboplastin time (PTT) within normal limits
5. Systolic blood pressure \<180 mm Hg and diastolic blood pressure \<100 mm Hg \[Note: Hypertension controlled by antihypertensive therapy is permitted\].
6. Willing and able to adhere to prohibitions and restrictions specified in this protocol
7. 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

Exclusion Criteria:

1. Prior treatment with 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, investigational agent, anticancer radiotherapy or anticancer endocrine therapy within 12 weeks before randomization
3. Use of hormone replacement therapy within the past 4 weeks
4. Serious or uncontrolled nonmalignant disease, including active or uncontrolled infection
5. Clinical or biochemical evidence of hyper-aldosteronism or hypopituitarism
6. 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
7. Major thoracic or abdominal surgery or significant traumatic injury with 4 weeks before randomization \[Note: Patients with planned surgical procedures to be conducted under local anesthesia are not excluded from the study (e.g. intravascular device insertion)\]
8. Gastrointestinal disorder interfering with study drug absorption
9. Positive serology for hepatitis B surface antigen or hepatitis C antibody
10. Active or symptomatic viral hepatitis or chronic liver disease
11. 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
12. Known allergies, hypersensitivity, or intolerance to abiraterone acetate, prednisone, or their excipients
13. 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

Primary outcomes:
measure: Differences in genomic expression and biological activity
timeFrame: 2 weeks (baseline and day 14)
Secondary outcomes:
measure: Change in proliferation
timeFrame: 2 weeks (baseline and day 14)
measure: Resulting adverse events of two weeks of abiraterone acetate
timeFrame: 2 weeks (baseline and day 14)
measure: Changes in plasma hormone levels
timeFrame: 2 weeks (baseline and day 14)
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver Centre
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Regional Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Segal Cancer Centre
state: Quebec
Study officials:
affiliation: British Columbia Cancer Agency
name: Stephen Chia, MD
role: PRINCIPAL_INVESTIGATOR
References: