The following datasets contain the data available for EPPT MDA2014-04-01. The description and documentation for each file is listed below. SAS7bdat and CSV versions of the actual data will be available to CDAS projects approved to use this study's data.

Analysis Datasets

Raw Datasets

These 49 datasets contain the raw form data received, excluding PII.

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Trial Summary

This phase IIb trial studies how well alternative dosing of exemestane before surgery works in treating in postmenopausal patients with stage 0-II estrogen positive breast cancer. Chemoprevention is the use of drugs to keep breast cancer from forming or coming back. The use of exemestane may treat early stage (stage 0-II) breast cancer. Comparing the exemestane standard dose regimen versus two alternative, less frequent dose regimens may decrease undesirable symptoms and have similar efficacy in reducing serum estradiol.

Participants are randomized to 1 of 3 treatment arms.

• ARM I: Participants receive exemestane orally (PO) once daily (QD) on days 1-7.
• ARM II: Participants receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7.
• ARM III: Participants receive exemestane PO QD on day 1 and placebo PO QD on days 2-7.

In all arms, cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity. Participants then undergo surgery on days 29, 36, or 43.

After completion of study treatment, patients are followed up at 20-30 days should any drug-related toxicity persists at final visit.

Target Enrollment: 300

Actual Enrollment: 230

Enrollment Statistics

Actual Registration: 230

• 180 people randomized
• 59 in Arm I (59 out of 180 randomized): Exemestane once daily
• 55 completed the study.
• 2 withdrew from study.
• 1 lost due to adverse events.
• 1 dropped due to other reasons.
• 58 in Arm II (58 out of 180 randomized): Exemestane three times a week
• 56 completed the study.
• 1 withdrew from study.
• 1 lost due to adverse events.
• 63 in Arm III (63 out of 180 randomized): Exemestane once weekly
• 60 completed the study.
• 1 withdrew from study.
• 1 lost due to adverse events.
• 1 dropped due to physicians decision.
• 50 people were not randomized (50 of 230 registered)

Statistical Analysis and Total Study Population Demographics:

• Age (years):
  • Mean: 64.3
  • Range: 45-82
  • Median: 64
• Height (cm):
  • Mean: 161
  • IQR: 156-165
  • Range: 146-177
  • Median: 161
• Weight (kg)
  • Mean: 76
  • IQR: 62-85
  • Range: 48-156
  • Median: 73
• Gender
  • Female: 180 (100%)

Eligibility Criteria

Inclusion Criteria

• Postmenopausal women (postmenopausal: age >= 60 years, or amenorrhea >= 12 months, or bilateral oophorectomy, or - in women with hysterectomy only - follicle stimulating hormone [FSH] in the menopausal levels as per local institutional guidelines if < 60 years old) with histologically-confirmed estrogen receptor (ER)-positive (>= 10%) primary breast cancer stage cT0-2, cN0-1, Mx; women with larger tumors who refuse chemotherapy (chemo) and/or endocrine neoadjuvant therapy can be eligible
• Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
• Leukocytes >= 3,000/microliter
• Absolute neutrophil count >= 1,500/microliter
• Platelets >= 100,000/microliter
• Total bilirubin =< 2 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional ULN
• Serum creatinine =< 1.5 times institutional ULN
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Body mass index (BMI) < 18.5 Kg/m^2
• Previous treatment for breast cancer including chemotherapy, endocrine therapy and radiotherapy; women with prior ductal breast carcinoma in situ (DCIS) who were treated with surgery only and whose treatment ended >= 2 years prior to enrollment are eligible for the trial
• Women who are planned to receive neoadjuvant therapy
• Participants may not be receiving investigational agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to exemestane
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Other co-existing invasive malignancies (with the exclusion of basal cell carcinoma or skin squamous cell carcinoma) diagnosed during the last 2 years before randomization
• History of severe osteoporosis (T score =< -4 either spine or hip), or presence of vertebral fracture
• Use of systemic hormone replacement therapy (HRT) in the last 30 days prior to the randomization; the use of non-systemic estrogen (such as vaginal estrogen use) is allowed
• Use of any chemopreventive agents (selective estrogen receptor modulators [SERM]) in the last 3 months
• Concomitant use of CYP3A4 inducer medication (rifampicin, phenytoin, carbamazepine, phenobarbital, and St. John's wort)

The Schema is a timeline of the study. It indicates start/end points, visits expected, major testing to be done, and any other information that is crucial to understanding how the study was completed.

A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was −89%, −85%, and −60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was −3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, −5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of −7.5%, −5.0%, and −4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and −17.0%, −9.0%, and −7.0% for progesterone receptor, respectively. Sex hormone–binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms.