- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02598557
Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer
Alternative Dosing of Exemestane in Postmenopausal Women With Stage 0-II ER-Positive Breast Cancer: A Randomized Presurgical Trial
Study Overview
Status
Conditions
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Genoa, Italy, 16128
- Galliera Hospital
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Milano, Italy, 20141
- European Institute of Oncology
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-
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Florida
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Tampa, Florida, United States, 33612
- Moffitt Cancer Center
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New York
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New York, New York, United States, 10032
- NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
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Texas
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Houston, Texas, United States, 77030
- M D Anderson Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Arm I: Exemestane 25 mg QD
Patients receive exemestane PO QD on days 1-7.
Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
Patients then undergo surgery on days 29, 36, or 43.
|
Correlative studies
Ancillary studies
Other Names:
Correlative studies
Ancillary studies
Undergo surgery
Given PO
Other Names:
|
Experimental: Arm II: Exemestane 25 TIW (exemestane, placebo)
Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7. Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
Patients then undergo surgery on days 29, 36, or 43.
|
Correlative studies
Ancillary studies
Other Names:
Correlative studies
Ancillary studies
Undergo surgery
Given PO
Given PO
Other Names:
|
Experimental: Arm III: Exemestane 25 mg QW (exemestane, placebo)
Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7.
Cycles repeat every 7 days for 4-6 weeks in the absence of disease progression or unacceptable toxicity.
Patients then undergo surgery on days 29, 36, or 43.
|
Correlative studies
Ancillary studies
Other Names:
Correlative studies
Ancillary studies
Undergo surgery
Given PO
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change in Time of Circulating Estradiol SPE in Each Arm
Time Frame: baseline and 4-6 weeks
|
LS means of percent change
|
baseline and 4-6 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change in Time of Circulating Estradiol LLE in Each Arm
Time Frame: baseline and 4-6 weeks
|
LS means of percent change
|
baseline and 4-6 weeks
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Percent Change of Circulating Estrone SPE
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Estrone LLE
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Total Estrone
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Estrone Sulfate
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Androstenedione
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Testosterone
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Testosterone CLIA
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating SHBG
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Total Cholesterol
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating HDL Cholesterol
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating LDL Cholesterol
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Triglycerides
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Insulin
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Serum Glucose
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of HOMA IR
Time Frame: baseline and 4-6 weeks
|
Insulin Resistance Index (HOMA-IR) measures insulin resistance, calculated by fasting insulin (mU/L) multiplied by fasting glucose (mmol/L), and divided by a constant (22.5).
A higher score indicates higher insulin resistance.
|
baseline and 4-6 weeks
|
Percent Change of Circulating Adiponectin
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Percent Change of Circulating Leptin
Time Frame: baseline and 4-6 weeks
|
[(Final levels-baseline levels)/baseline levels]*100
|
baseline and 4-6 weeks
|
Exemestane Blood Concentration at Surgery
Time Frame: at surgery
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Final drug concentration
|
at surgery
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17-OH Exemestane Blood Concentration at Surgery
Time Frame: at surgery
|
Final drug concentration
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at surgery
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Change of ER Expression (Cancer Tissue), Central Review
Time Frame: 4-6 weeks
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Surgery level-biopsy level.
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4-6 weeks
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Change of PgR Expression (Cancer Tissue), Central Review
Time Frame: 4-6 weeks
|
Surgery level-biopsy level.
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4-6 weeks
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Change of Ki67% Expression (Cancer Tissue), Central Review
Time Frame: 4-6 weeks
|
Surgery level-biopsy level.
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4-6 weeks
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Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review
Time Frame: 4-6 weeks
|
Surgery level-biopsy level.
|
4-6 weeks
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Estradiol Tissue Concentration at Surgery
Time Frame: 4-6 weeks
|
Final biomarker concentration
|
4-6 weeks
|
Estrone Tissue Concentration at Surgery
Time Frame: 4-6 weeks
|
Final biomarker concentration
|
4-6 weeks
|
Androstenedione Tissue Concentration at Surgery
Time Frame: 4-6 weeks
|
Final biomarker concentration.
|
4-6 weeks
|
Testosterone Tissue Concentration at Surgery
Time Frame: 4-6 weeks
|
Final biomarker concentration
|
4-6 weeks
|
Exemestane Tissue Concentration at Surgery
Time Frame: 4-6 weeks
|
Final drug concentration
|
4-6 weeks
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17 OH Exemestane Tissue Concentration at Surgery
Time Frame: 4-6 weeks
|
Final drug concentration
|
4-6 weeks
|
Change in MenQoL Questionnaire Score
Time Frame: baseline and 4-6 weeks
|
MenQOL questionnaire assessed how bothered participants were with 31 symptoms.
It contains domains: vasomotor (items 1-3); psychosocial (items 4-10); physical (items 11-26); sexual (items 27-29); in addition to nausea and indigestion.
31 individual symptoms are rated on a scale of 0 (not at all bothered) to 6 (extremely bothered).
Total possible score ranged from 0 to 186.
MenQOL summary score was calculated as mean of four domain scores (Physical function, Psychosocial function, Sexual function and Vasomotor function) ranging from 1 to 8, with higher scores indicating worse quality of life.
Final score-baseline score
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baseline and 4-6 weeks
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proteomic Analysis
Time Frame: 4-6 weeks
|
The Proteomic Analysis was not performed.
|
4-6 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Bernardo Bonanni, European Institute of Oncology
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Breast Diseases
- Carcinoma in Situ
- Breast Neoplasms
- Breast Carcinoma In Situ
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Exemestane
Other Study ID Numbers
- NCI-2015-01821 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- P30CA016672 (U.S. NIH Grant/Contract)
- N01-CN-2012-00034 (CTRP (Clinical Trial Reporting Program))
- N01CN00034 (U.S. NIH Grant/Contract)
- HHSN26120120034I
- 2016-0276 (Other Identifier: M D Anderson Cancer Center)
- MDA2014-04-01 (Other Identifier: DCP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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