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

Status: Active

Description

This randomized 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.

Eligibility Criteria

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)

Locations & Contacts

Florida

Tampa
Moffitt Cancer Center
Status: Active
Contact: Nagi B. Kumar
Phone: 813-745-6885
Email: nagi.kumar@moffitt.org

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Contact: Katherine D. Crew
Phone: 212-305-1732
Email: kd59@cumc.columbia.edu

Texas

Houston
M D Anderson Cancer Center
Status: Active
Contact: Powel H. Brown
Phone: 713-792-4509
Email: phbrown@mdanderson.org

Italy

Genoa
Galliera Hospital
Status: Active
Contact: Andrea De Censi
Phone: 39-010 5634501
Email: andrea.decensi@galliera.it
Milano
European Institute of Oncology
Status: Active
Contact: Bernardo Bonanni
Phone: 39-0257489022
Email: bernardo.bonanni@ieo.it

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. Non-inferiority of percent change in time of serum estradiol levels, adjusted for baseline levels, following four up to six weeks of exemestane 25 mg given three times per week or one time per week compared with exemestane 25 mg daily dosing.

SECONDARY OBJECTIVES:

I. To assess safety and toxicity.

II. To support the preventive activity of exemestane we will investigate the change in Ki-67 and progesterone receptor (PgR) levels in tumor cells and the adjacent intraepithelial neoplasia or benign histologic structures.

III. To assess possible association of estradiol level with tissue and circulating biomarkers.

IV. To investigate possible pharmacogenetic markers.

V. To assess drug levels on tissue samples.

VI. To investigate tissue and circulating proteomics profiling.

OUTLINE: Patients are randomized to 1 of 3 treatment arms.

ARM I: Patients receive exemestane orally (PO) once daily (QD) on days 1-7.

ARM II: Patients receive exemestane PO QD on days 1, 3, and 5. Patients also receive placebo PO QD on days 2, 4, 6, and 7.

ARM III: Patients receive exemestane PO QD on day 1 and placebo PO QD on days 2-7.

In all arms, courses 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.

After completion of study treatment, patients are followed up at 20-30 days.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Prevention

Lead Organization

Lead Organization
M D Anderson Cancer Center

Principal Investigator
Bernardo Bonanni

Trial IDs

Primary ID 2016-0276
Secondary IDs MDA2014-04-01, NCI-2015-01821, N01-CN-2012-00034, HHSN26120120034I
Clinicaltrials.gov ID NCT02598557