Clinical trial NCT02598557: Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer
Official title: Alternative Dosing of Exemestane in Postmenopausal Women With Stage 0-II ER-Positive Breast Cancer: A Randomized Presurgical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage 0 Breast Cancer AJCC v6 and v7
Stage I Breast Cancer AJCC v7
Stage IA Breast Cancer AJCC v7
Stage IB Breast Cancer AJCC v7
Stage II Breast Cancer AJCC v6 and v7
Stage IIA Breast Cancer AJCC v6 and v7
Stage IIB Breast Cancer AJCC v6 and v7
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2015-11-06
Enrollment: 180
Sex: FEMALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: We have conducted an international, multicenter, pre-surgical double-blind non-inferiority phase IIb study in which a total of 180 participants have been randomized to receive either exemestane 25 mg/day (Exemestane 25 mg QD) or 25 mg/ three times a week (Exemestane 25 mg TIW) or a single dose of 25 mg/week (Exemestane 25 mg QW) for a minimum of 4 up to 6 weeks. Participants were stratified by center and BMI (\<25 kg/m2 vs \>25 kg/m2).

Participants were histologically confirmed ER-positive (ER \>10%) primary breast cancer patients who were candidates for breast surgery. Postmenopausal women younger than 76 years of age with cT0-2, cN0-1, Mx or women with larger tumors who refuse neo-adjuvant therapy before surgery were eligible. No previous treatment for breast cancer was allowed.

Complete physical exam and safety lab tests have been performed at baseline and at the end of treatment (28+1, 35+1, 42+1 days). Phone contact occurred on day 1 and a week before surgery (+3 days). Participants experiencing persistent adverse events (certainly, probably, and possibly treatment-related) have been monitored 20-30 days after study completion.

Biomarkers: blood samples were collected at baseline and the end of treatment (fasting blood for biomarkers collected prior to randomization and either on the day of surgery or the day before; fasting strongly recommended but not mandated), tissue samples collected from the diagnostic or research biopsy and at the time of surgery.

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)

Primary outcomes:
measure: Percent Change in Time of Circulating Estradiol SPE in Each Arm
timeFrame: baseline and 4-6 weeks
Secondary outcomes:
measure: Percent Change in Time of Circulating Estradiol LLE in Each Arm
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Estrone SPE
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Estrone LLE
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Total Estrone
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Estrone Sulfate
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Androstenedione
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Testosterone
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Testosterone CLIA
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating SHBG
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Total Cholesterol
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating HDL Cholesterol
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating LDL Cholesterol
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Triglycerides
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Insulin
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Serum Glucose
timeFrame: baseline and 4-6 weeks
measure: Percent Change of HOMA IR
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Adiponectin
timeFrame: baseline and 4-6 weeks
measure: Percent Change of Circulating Leptin
timeFrame: baseline and 4-6 weeks
measure: Exemestane Blood Concentration at Surgery
timeFrame: at surgery
measure: 17-OH Exemestane Blood Concentration at Surgery
timeFrame: at surgery
measure: Change of ER Expression (Cancer Tissue), Central Review
timeFrame: 4-6 weeks
measure: Change of PgR Expression (Cancer Tissue), Central Review
timeFrame: 4-6 weeks
measure: Change of Ki67% Expression (Cancer Tissue), Central Review
timeFrame: 4-6 weeks
measure: Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review
timeFrame: 4-6 weeks
measure: Estradiol Tissue Concentration at Surgery
timeFrame: 4-6 weeks
measure: Estrone Tissue Concentration at Surgery
timeFrame: 4-6 weeks
measure: Androstenedione Tissue Concentration at Surgery
timeFrame: 4-6 weeks
measure: Testosterone Tissue Concentration at Surgery
timeFrame: 4-6 weeks
measure: Exemestane Tissue Concentration at Surgery
timeFrame: 4-6 weeks
measure: 17 OH Exemestane Tissue Concentration at Surgery
timeFrame: 4-6 weeks
measure: Change in MenQoL Questionnaire Score
timeFrame: baseline and 4-6 weeks
Other outcomes:
measure: Proteomic Analysis
timeFrame: 4-6 weeks
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: New York
country: United States
facility: NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
state: New York
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
city: Genoa
country: Italy
facility: Galliera Hospital
city: Milano
country: Italy
facility: European Institute of Oncology
Study officials:
affiliation: European Institute of Oncology
name: Bernardo Bonanni
role: PRINCIPAL_INVESTIGATOR
References: