NCT02598557

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
180

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Dec 2016

Longer than P75 for phase_2

Geographic Reach
2 countries

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 5, 2015

Completed
1 day until next milestone

First Posted

Study publicly available on registry

November 6, 2015

Completed
1.1 years until next milestone

Study Start

First participant enrolled

December 6, 2016

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 3, 2019

Completed
3.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 2, 2023

Completed
7 months until next milestone

Results Posted

Study results publicly available

August 22, 2023

Completed
Last Updated

August 22, 2023

Status Verified

August 1, 2023

Enrollment Period

2.8 years

First QC Date

November 5, 2015

Results QC Date

March 31, 2023

Last Update Submit

August 3, 2023

Conditions

Outcome Measures

Primary Outcomes (1)

  • Percent Change in Time of Circulating Estradiol SPE in Each Arm

    LS means of percent change

    baseline and 4-6 weeks

Secondary Outcomes (31)

  • Percent Change in Time of Circulating Estradiol LLE in Each Arm

    baseline and 4-6 weeks

  • Percent Change of Circulating Estrone SPE

    baseline and 4-6 weeks

  • Percent Change of Circulating Estrone LLE

    baseline and 4-6 weeks

  • Percent Change of Circulating Total Estrone

    baseline and 4-6 weeks

  • Percent Change of Circulating Estrone Sulfate

    baseline and 4-6 weeks

  • +26 more secondary outcomes

Other Outcomes (1)

  • Proteomic Analysis

    4-6 weeks

Study Arms (3)

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.

Drug: ExemestaneOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationProcedure: 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.

Drug: ExemestaneOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Placebo AdministrationOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationProcedure: 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.

Drug: ExemestaneOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Placebo AdministrationOther: Quality-of-Life AssessmentOther: Questionnaire AdministrationProcedure: Therapeutic Conventional Surgery

Interventions

Given PO

Also known as: Aromasin, FCE-24304
Arm I: Exemestane 25 mg QDArm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Correlative studies

Arm I: Exemestane 25 mg QDArm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Correlative studies

Arm I: Exemestane 25 mg QDArm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Given PO

Arm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Ancillary studies

Also known as: Quality of Life Assessment
Arm I: Exemestane 25 mg QDArm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Ancillary studies

Arm I: Exemestane 25 mg QDArm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Undergo surgery

Arm I: Exemestane 25 mg QDArm II: Exemestane 25 TIW (exemestane, placebo)Arm III: Exemestane 25 mg QW (exemestane, placebo)

Eligibility Criteria

AgeUp to 75 Years
Sexfemale
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

New York, New York, 10032, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Galliera Hospital

Genoa, 16128, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Related Publications (2)

  • 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.

  • 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.

Related Links

MeSH Terms

Conditions

Breast Carcinoma In SituBreast Neoplasms

Interventions

exemestane

Condition Hierarchy (Ancestors)

Carcinoma in SituCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsNeoplasms by SiteBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Results Point of Contact

Title
Parijatham S. Thomas, MD., Associate Professor, Clinical Cancer Prevention
Organization
UT MD Anderson Cancer Center

Study Officials

  • Bernardo Bonanni

    European Institute of Oncology

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 5, 2015

First Posted

November 6, 2015

Study Start

December 6, 2016

Primary Completion

October 3, 2019

Study Completion

February 2, 2023

Last Updated

August 22, 2023

Results First Posted

August 22, 2023

Record last verified: 2023-08

Locations