Stage 0 Breast Cancer AJCC v6 and v7Phase 2NCT02598557

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

A Phase 2 study testing Exemestane, Laboratory Biomarker Analysis and Pharmacological Study in people with Stage 0 Breast Cancer AJCC v6 and v7 and Stage I Breast Cancer AJCC v7, run by National Cancer Institute (NCI) at 5 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages Up to 75 years, women only
Conditions the study is for: Stage 0 Breast Cancer AJCC v6 and v7, Stage I Breast Cancer AJCC v7, Stage IA Breast Cancer AJCC v7
What is being tested?: Exemestane, Laboratory Biomarker Analysis and Pharmacological Study
Type of treatment: Surgery or procedure
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 180 participants
Where: 5 sitesin 2 countries
Study dates: 6 Dec 2016to 2 Feb 2023
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Up to 75 years
Women only
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

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)

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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

Who cannot join

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

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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)

Trial locations and contacts

5 sites in 2 countries.

Country

City, postcode or hospital

5 sites in 2 countries

United States3 sites

M D Anderson Cancer Center
Houston, Texas, 77030
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Moffitt Cancer Center
Tampa, Florida, 33612

Other trials in United States

Italy2 sites

Galliera Hospital
Genoa, 16128
European Institute of Oncology
Milan, 20141

Other trials in Italy

About this study

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

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.

Read the 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.

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
Being tested: Exemestane, Laboratory Biomarker Analysis, Pharmacological Study, Placebo Administration, Quality-of-Life Assessment
Medical subject headings: Breast Carcinoma In Situ, Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

ExemestaneDrug
Also called Aromasin, FCE-24304
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Pharmacological StudyOther
Correlative studies
Placebo AdministrationOther
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Ancillary studies
Questionnaire AdministrationOther
Ancillary studies
Therapeutic Conventional SurgeryProcedure or surgery
Undergo surgery

Study groups in NCT02598557
Study group	Role	What they receive
Arm I: Exemestane 25 mg QD	Experimental	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. Receives: Drug: Exemestane; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Therapeutic Conventional Surgery
Arm II: Exemestane 25 TIW (exemestane, placebo)	Experimental	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. Receives: Drug: Exemestane; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Therapeutic Conventional Surgery
Arm III: Exemestane 25 mg QW (exemestane, placebo)	Experimental	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. Receives: Drug: Exemestane; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Procedure: Therapeutic Conventional Surgery

What is being measured

The primary outcome is the main question the study is designed to answer.

Percent Change in Time of Circulating Estradiol SPE in Each Arm
LS means of percent change
Measured: baseline and 4-6 weeks

Secondary outcomes (31)

Percent Change in Time of Circulating Estradiol LLE in Each Arm
LS means of percent change
Measured: baseline and 4-6 weeks
Percent Change of Circulating Estrone SPE
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Estrone LLE
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Total Estrone
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Estrone Sulfate
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Androstenedione
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Testosterone
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Testosterone CLIA
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating SHBG
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Total Cholesterol
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating HDL Cholesterol
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating LDL Cholesterol
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Triglycerides
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Insulin
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Serum Glucose
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
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.
Measured: baseline and 4-6 weeks
Percent Change of Circulating Adiponectin
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Percent Change of Circulating Leptin
[(Final levels-baseline levels)/baseline levels]*100
Measured: baseline and 4-6 weeks
Exemestane Blood Concentration at Surgery
Final drug concentration
Measured: at surgery
17-OH Exemestane Blood Concentration at Surgery
Final drug concentration
Measured: at surgery
Change of ER Expression (Cancer Tissue), Central Review
Surgery level-biopsy level.
Measured: 4-6 weeks
Change of PgR Expression (Cancer Tissue), Central Review
Surgery level-biopsy level.
Measured: 4-6 weeks
Change of Ki67% Expression (Cancer Tissue), Central Review
Surgery level-biopsy level.
Measured: 4-6 weeks
Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review
Surgery level-biopsy level.
Measured: 4-6 weeks
Estradiol Tissue Concentration at Surgery
Final biomarker concentration
Measured: 4-6 weeks
Estrone Tissue Concentration at Surgery
Final biomarker concentration
Measured: 4-6 weeks
Androstenedione Tissue Concentration at Surgery
Final biomarker concentration.
Measured: 4-6 weeks
Testosterone Tissue Concentration at Surgery
Final biomarker concentration
Measured: 4-6 weeks
Exemestane Tissue Concentration at Surgery
Final drug concentration
Measured: 4-6 weeks
17 OH Exemestane Tissue Concentration at Surgery
Final drug concentration
Measured: 4-6 weeks
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
Measured: baseline and 4-6 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

6 Dec 20162 Feb 2023

First posted6 Nov 2015 (estimated)
Study start6 Dec 2016
Primary completion3 Oct 2019
Study completion2 Feb 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Stage 0 Breast Cancer AJCC v6 and v7Studies of the same condition, open and under way.
More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 180 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02598557
Sponsor's protocol ID: NCI-2015-01821
Other IDs: NCI-2015-01821, HHSN26120120034I, N01-CN-2012-00034, 2016-0276, MDA2014-04-01, N01CN00034, P30CA016672
Status last verified: Aug 2023
First submitted: 5 Nov 2015
Last updated: 22 Aug 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Serrano D, Johansson H, Bertelsen BE, Gandini S, Mellgren G, Thomas P, Crew KD, Kumar NB, Macis D, Aristarco V, Guerrieri-Gonzaga A, Lazzeroni M, D'Amico M, Buttiron-Webber T, Briata IM, Spinaci S, Galimberti V, Vornik LA, Vilar E, Brown PH, Heckman-Stoddard BM, Szabo E, Bonanni B, DeCensi A. Drug and biomarker tissue levels in a randomized presurgical trial on exemestane alternative schedules. J Natl Cancer Inst. 2024 Dec 1;116(12):1979-1982. doi: 10.1093/jnci/djae183.
PubMed 39110531
Serrano D, Gandini S, Thomas P, Crew KD, Kumar NB, Vornik LA, Lee JJ, Veronesi P, Viale G, Guerrieri-Gonzaga A, Lazzeroni M, Johansson H, D'Amico M, Guasone F, Spinaci S, Bertelsen BE, Mellgren G, Bedrosian I, Weber D, Castile T, Dimond E, Heckman-Stoddard BM, Szabo E, Brown PH, DeCensi A, Bonanni B. Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial. JAMA Oncol. 2023 May 1;9(5):664-672. doi: 10.1001/jamaoncol.2023.0089.
PubMed 36951827

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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