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Conjugated Estrogens / Bazedoxifene in Treating Patients with Ductal Carcinoma in Situ Undergoing Surgery

Trial Status: Active

The main purpose of this study is to determine if taking the study drug, conjugated estrogens / bazedoxifene (Duavee) causes any changes in the proliferation markers within the breast tissue of the study subjects. The study drug is approved by the US Food and Drug Administration in healthy postmenopausal women to treat certain symptoms of menopause such as hot flashes. Since it is not approved in women with ductal carcinoma in situ (DCIS), its use in this study is experimental. This study will also look at whether taking the study drug causes any significant or undesirable side effects in women with DCIS. The researchers hope that this study will help them determine if taking the study drug is safe in women taking DCIS and if it can possibly reduce the risk of developing breast cancer in women with DCIS.

Inclusion Criteria

  • Women must have newly diagnosed histologically confirmed ER positive (+) DCIS scheduled to undergo surgical therapy; the pathology report (signed pathology report from attending pathologist) from each individual institution will be used to determine eligibility; extent of DCIS in imaging per site institutional standard * Note: After the patient has completed the study and the slides have been sent to Northwestern University (NU), our pathologists will review the slides to confirm the diagnosis * Note: DCIS suspicious for micro invasion is eligible on core biopsy * Note: Women presenting with bilateral DCIS are eligible but if both right and left DCIS are ER+, we will only accept tissue from the side with the largest area of DCIS based on imaging and pathology criteria
  • DCIS must be >= 1 cm based on extent of calcifications, presence of a mass on ultrasound OR enhancement on magnetic resonance imaging (MRI) OR
  • DCIS must be >= 5 mm of DCIS on one single core; can be < 5 mm if DCIS is identified on multiple cores (at least 2 cores)
  • Women presenting after excision with positive margins are eligible; Ki-67, cyclooxygenase 2 (Cox-2), cyclin-dependent kinase inhibitor 2A (P-16), expression in immediately adjacent tissue is similar to what is found in DCIS * Note: Positive margins are defined as DCIS present at the inked margin or DCIS < 1 mm from the margin
  • Women must be postmenopausal (defined as no menstrual cycle for 12 months or surgical history of bilateral salpingoopherectomy); postmenopausal women of all races and ethnic groups are eligible to participate for this trial; men are not eligible * Note: women who have had a hysterectomy without a bilateral salpingoopherectomy may still be pre-menopausal; confirmation of post-menopausal status is required for these patients and will be measured by testing levels of estradiol, progesterone and follicle stimulating hormone (FSH) (lab ranges per institutional standards); in addition, confirmation of postmenopausal status may be performed in any patient with unclear menopausal status per treating physician discretion
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
  • Leukocytes >= 3,000/mcL
  • Platelets >= 100,000/mcL
  • Hemoglobin >= 9 g/dl
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate [SGPT]) =< 2.5 x institutional upper limit of normal
  • Serum creatinine =< 1.5 x ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels above institutional normal (calculated with the Cockcroft-Gault Equation in EPIC)
  • Patients ability to swallow oral medication
  • Ability to understand and the willingness to sign a written informed consent document and comply with all procedures

Exclusion Criteria

  • Patients who are receiving any other investigational agents; a minimum of 4 weeks wash-out period is required for eligibility; please contact principal investigator, Dr. Swati Kulkarni for further clarification
  • Patients with a “currently active” second malignancy other than non-melanoma skin cancers; patients are not considered to have a “currently active” malignancy if they have completed therapy and are free of disease for >= 3 years
  • History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to CE/BZA; (I.e. same class of drug as CE/BZA)
  • Current hormone replacement therapy (HRT), selective estrogen receptor modulator (SERM) or aromatase inhibitor (AI) use; if yes, the wash-out period is 30 days before diagnostic core needle biopsy * Note: local therapy (i.e. estrogen cream) will be permitted due to low systemic absorption of estrogen * Note: if patient is registered prior to completed washout, diagnostic core needle biopsy date will need to be provided
  • Confirmed current or past diagnosis of invasive breast cancer
  • History of gynecologic malignancy that is estrogen dependent
  • Patients with recurrent ipsilateral DCIS
  • Active deep venous thrombosis, pulmonary embolism, retinal vascular thrombosis, and any arterial thrombosis including stroke and myocardial infarction or history of these conditions
  • Known protein C, protein S, or anti-thrombin deficiency or other known thrombophilic disorders
  • Unexplained/undiagnosed abnormal uterine bleeding (concern for undiagnosed endometrial cancer)
  • Women who are pregnant or lactating, if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus
  • Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 and UGT are ineligible; the wash out period for such drugs is a minimum of 7 days or 5 half-lives whichever is shorter * Note: If a medication is incorrectly documented as prohibited in this protocol, documentation from the site pharmacist to the contrary will be acceptable for the purposes of registration
  • 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

California

Los Angeles
USC / Norris Comprehensive Cancer Center
Status: CLOSED_TO_ACCRUAL_AND_INTERVENTION
Contact: Julie Eileen Lang
Phone: 323-442-5510
San Francisco
UCSF Medical Center-Parnassus
Status: IN_REVIEW
Contact: Thea D. Tlsty
Phone: 415-502-6115

Colorado

Denver
University of Colorado
Status: ACTIVE
Contact: Gretchen McGuire Ahrendt
Phone: 303-724-8366

Illinois

Chicago
Northwestern University
Status: ACTIVE
Contact: Swati A. Kulkarni
Phone: 312-503-2899
University of Chicago Comprehensive Cancer Center
Status: IN_REVIEW
Contact: Geoffrey Greene
Phone: 773-702-6964
Geneva
Northwestern Medicine Cancer Center Delnor
Status: ACTIVE
Contact: Swati A. Kulkarni
Phone: 312-503-2899

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: ACTIVE
Contact: David M. Euhus
Phone: 410-955-2803

Massachusetts

Boston
Dana-Farber Cancer Institute
Status: ACTIVE
Contact: Judy Ellen Garber
Phone: 617-632-2282

Missouri

Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Rebecca L. Aft
Phone: 314-747-0063

Pennsylvania

Philadelphia
Thomas Jefferson University Hospital
Status: ACTIVE
Contact: Melissa Ann Lazar
Phone: 215-955-6999
University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE
Contact: Julia C. Tchou
Phone: 215-615-7575
Pittsburgh
UPMC-Magee Womens Hospital
Status: ACTIVE
Contact: Emilia J. Diego
Phone: 412-641-4274

PRIMARY OBJECTIVES:

I. To determine if conjugated estrogens/bazedoxifene (CE/BZA) reduces proliferation as measured by Ki-67 protein expression.

SECONDARY OBJECTIVES:

I. To determine if CE/BZA modulates expression of estrogen receptor (ER)alpha, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2).

II. To determine if CE/BZA modulates a previously validated set of epithelial markers of progression.

III. To determine if tissue selective estrogen complexes (TSECs) will restore expression of the stromal marker CD36 and repress pro-tumorigenic extracellular matrix (ECM) proteins and soluble factors.

IV. To determine if a short intervention with CE/BZA results in any difference in quality of life (QOL) as it relates to menopausal symptoms in postmenopausal women with DCIS.

V. To determine if a short intervention with CE/BZA has a favorable side effect profile compared with other endocrine therapy interventions using the validated Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire.

EXPLORATORY OBJECTIVES:

I. To determine if CE/BZA alters expression of estrogen-modulated genes and elicits novel ER dependent-gene signatures in breast epithelium.

II. To demonstrate that CE/BZA does not upregulate Anterior Gradient 2 (AGR2), a marker of ERalpha agonist activity.

III. To determine if CE/BZA will modulate some aspects of immune function as measured by a switch to a M2-type pro-tumorigenic macrophage signature and an immunosuppressive T cell signature.

IV. To determine if a short intervention with CE/BZA alters expression of estrogen-modulated genes and elicits novel ER dependent-gene signatures in the breast stroma.

V. To determine if CE/BZA affects plasma concentrations of BZA in patients with the UGT1A1*28 gene polymorphism.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive conjugated estrogens/bazedoxifene orally (PO) once daily (QD) on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

ARM II: Patients receive placebo PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

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

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Northwestern University

Principal Investigator
Swati A. Kulkarni

  • Primary ID NU 15B06
  • Secondary IDs NCI-2016-00066, STU00202100
  • Clinicaltrials.gov ID NCT02694809