Alternative Dosing of Exemestane Before Surgery in Treating Postmenopausal Patients With Stage 0-II Estrogen Positive Breast Cancer

Stage IIB Breast Cancer AJCC v6 and v7 Clinical Trial

Official title:

Alternative Dosing of Exemestane in Postmenopausal Women With Stage 0-II ER-Positive Breast Cancer: A Randomized Presurgical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02598557
• Other study ID #: NCI-2015-01821
• Secondary ID: NCI-2015-01821HH
• Status: Completed
• Phase: Phase 2
• Start date: December 6, 2016
• Est. completion date: February 2, 2023

Study information

• Verified date: August 2023
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 180
• Est. completion date: February 2, 2023
• Est. primary completion date: October 3, 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Breast Carcinoma In Situ
• Breast Neoplasms
• 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

Intervention

Drug:
• Exemestane
Given PO

Other:
• Laboratory Biomarker Analysis
Correlative studies
• Pharmacological Study
Correlative studies
• Placebo Administration
Given PO
• Quality-of-Life Assessment
Ancillary studies
• Questionnaire Administration
Ancillary studies

Procedure:
• Therapeutic Conventional Surgery
Undergo surgery

Locations

Country	Name	City	State
Italy	Galliera Hospital	Genoa
Italy	European Institute of Oncology	Milano
United States	M D Anderson Cancer Center	Houston	Texas
United States	NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center	New York	New York
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proteomic Analysis	The Proteomic Analysis was not performed.	4-6 weeks
Primary	Percent Change in Time of Circulating Estradiol SPE in Each Arm	LS means of percent change	baseline and 4-6 weeks
Secondary	Percent Change in Time of Circulating Estradiol LLE in Each Arm	LS means of percent change	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Estrone SPE	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Estrone LLE	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Total Estrone	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Estrone Sulfate	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Androstenedione	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Testosterone	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Testosterone CLIA	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating SHBG	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Total Cholesterol	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating HDL Cholesterol	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating LDL Cholesterol	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Triglycerides	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Insulin	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Serum Glucose	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of HOMA IR	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
Secondary	Percent Change of Circulating Adiponectin	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Percent Change of Circulating Leptin	[(Final levels-baseline levels)/baseline levels]*100	baseline and 4-6 weeks
Secondary	Exemestane Blood Concentration at Surgery	Final drug concentration	at surgery
Secondary	17-OH Exemestane Blood Concentration at Surgery	Final drug concentration	at surgery
Secondary	Change of ER Expression (Cancer Tissue), Central Review	Surgery level-biopsy level.	4-6 weeks
Secondary	Change of PgR Expression (Cancer Tissue), Central Review	Surgery level-biopsy level.	4-6 weeks
Secondary	Change of Ki67% Expression (Cancer Tissue), Central Review	Surgery level-biopsy level.	4-6 weeks
Secondary	Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review	Surgery level-biopsy level.	4-6 weeks
Secondary	Estradiol Tissue Concentration at Surgery	Final biomarker concentration	4-6 weeks
Secondary	Estrone Tissue Concentration at Surgery	Final biomarker concentration	4-6 weeks
Secondary	Androstenedione Tissue Concentration at Surgery	Final biomarker concentration.	4-6 weeks
Secondary	Testosterone Tissue Concentration at Surgery	Final biomarker concentration	4-6 weeks
Secondary	Exemestane Tissue Concentration at Surgery	Final drug concentration	4-6 weeks
Secondary	17 OH Exemestane Tissue Concentration at Surgery	Final drug concentration	4-6 weeks
Secondary	Change in MenQoL Questionnaire Score	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	baseline and 4-6 weeks

External Links

•   MD Anderson Cancer Center