AzTrials
AzTrials

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
Search all trials

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. Read more about this study

Who is it for?
Ages Up to 75 years, women only
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
Are there results?
Yes, posted in the registrySummary in the doctors' view

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)
Show all 9Show fewer
  • 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
Show all 11Show fewer
  • 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.

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.

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 groupRoleWhat they receive
Arm I: Exemestane 25 mg QDExperimentalPatients 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)ExperimentalPatients 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)ExperimentalPatients 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.

  1. 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)

  1. Percent Change in Time of Circulating Estradiol LLE in Each Arm

    LS means of percent change

    Measured: baseline and 4-6 weeks

  2. Percent Change of Circulating Estrone SPE

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  3. Percent Change of Circulating Estrone LLE

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  4. Percent Change of Circulating Total Estrone

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  5. Percent Change of Circulating Estrone Sulfate

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  6. Percent Change of Circulating Androstenedione

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  7. Percent Change of Circulating Testosterone

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  8. Percent Change of Circulating Testosterone CLIA

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  9. Percent Change of Circulating SHBG

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  10. Percent Change of Circulating Total Cholesterol

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  11. Percent Change of Circulating HDL Cholesterol

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  12. Percent Change of Circulating LDL Cholesterol

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  13. Percent Change of Circulating Triglycerides

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  14. Percent Change of Circulating Insulin

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  15. Percent Change of Serum Glucose

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  16. 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

  17. Percent Change of Circulating Adiponectin

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  18. Percent Change of Circulating Leptin

    [(Final levels-baseline levels)/baseline levels]*100

    Measured: baseline and 4-6 weeks

  19. Exemestane Blood Concentration at Surgery

    Final drug concentration

    Measured: at surgery

  20. 17-OH Exemestane Blood Concentration at Surgery

    Final drug concentration

    Measured: at surgery

  21. Change of ER Expression (Cancer Tissue), Central Review

    Surgery level-biopsy level.

    Measured: 4-6 weeks

  22. Change of PgR Expression (Cancer Tissue), Central Review

    Surgery level-biopsy level.

    Measured: 4-6 weeks

  23. Change of Ki67% Expression (Cancer Tissue), Central Review

    Surgery level-biopsy level.

    Measured: 4-6 weeks

  24. Change of Ki67% Expression (Adjacent Non Cancer Tissue), Central Review

    Surgery level-biopsy level.

    Measured: 4-6 weeks

  25. Estradiol Tissue Concentration at Surgery

    Final biomarker concentration

    Measured: 4-6 weeks

  26. Estrone Tissue Concentration at Surgery

    Final biomarker concentration

    Measured: 4-6 weeks

  27. Androstenedione Tissue Concentration at Surgery

    Final biomarker concentration.

    Measured: 4-6 weeks

  28. Testosterone Tissue Concentration at Surgery

    Final biomarker concentration

    Measured: 4-6 weeks

  29. Exemestane Tissue Concentration at Surgery

    Final drug concentration

    Measured: 4-6 weeks

  30. 17 OH Exemestane Tissue Concentration at Surgery

    Final drug concentration

    Measured: 4-6 weeks

  31. 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.

  1. First posted6 Nov 2015 (estimated)
  2. Study start6 Dec 2016
  3. Primary completion3 Oct 2019
  4. Study completion2 Feb 2023

Resources

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
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

Questions about this trial

What is this clinical trial studying?

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.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Aug 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent Change in Time of Circulating Estradiol SPE in Each Arm (time frame: baseline and 4-6 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02598557, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in