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Eligibility
for females ages 18 years to 75 years
Location
at San Francisco, California and other locations
Dates
study started

Description

Summary

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 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.

Official Title

A Phase II Randomized-double Blinded Placebo Controlled Window of Opportunity Trial Comparing Conjugated Estrogens/Bazedoxifene to Placebo in Women Undergoing Surgical Therapy for Ductal Carcinoma in Situ (DCIS)

Details

PRIMARY OBJECTIVES; I. To assess whether CE/BZA (conjugated estrogens/bazedoxifene) for 28 days +/- 7 days reduces proliferation as measured by marker of proliferation Ki-67 (Ki-67) protein expression.

SECONDARY OBJECTIVES:

I. To assess whether CE/BZA alters markers associated with progression to invasive cancer (abrogated response to cellular stress [ARCS] signature) in postmenopausal women with ductal carcinoma in situ [DCIS] compared to placebo).

II. To assess changes in quality of life (QOL) using the Menopause-specific Quality of Life (MENQOL) questionnaire at baseline and at the conclusion of the intervention in women with DCIS treated with CE/BZA compared to placebo.

TERTIARY OBJECTIVES:

I. To assess changes in the stromal marker cluster of differentiation (CD)36, in women with DCIS with CE/BZA compared to placebo.

II. To assess changes in hormone receptor (estrogen receptor alpha [ERa] and progesterone receptor [PR]) expression in women with DCIS treated with CE/BZA compared to placebo.

III. To assess changes in global gene expression profiling (ribonucleic acid [RNA] sequencing) in women with DCIS treated with CE/BZA compared to placebo.

IV. To identify possible polymorphisms that may affect the metabolism of CE/BZA.

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 for 30 days.

Keywords

Ductal Breast Carcinoma In Situ Postmenopausal Estrogens Estrogens, Conjugated (USP) Bazedoxifene

Eligibility

You can join if…

Open to females ages 18 years to 75 years

  • Women must have newly diagnosed histologically confirmed 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;(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)
  • DCIS suspicious for micro invasion is eligible on core biopsy; this is due to the fact that many these patients will not have invasion on final pathology
  • DCIS must be greater than 1 cm based on extent of calcifications, presence of a mass on ultrasound OR enhancement on magnetic resonance imaging (MRI)
  • DCIS must be at least 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
  • Women must be postmenopausal (defined as no menstrual cycle for 12 months or surgical history of bilateral salpingo-oopherectomy); postmenopausal women of all races and ethnic groups are eligible to participate for this trial; men are not eligible
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky>= 60%)
  • Leukocytes>= 3,000/mcL
  • Absolute neutrophil count>= 1,500/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 ×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
  • Body mass index (BMI) < 35; a reduction in BZA exposure may be seen in obese women based pharmacokinetic modeling from previous studies
  • Patients ability to swallow oral medication
  • Ability to understand and the willingness to sign a written informed consent document and comply with all procedures

You CAN'T join if...

  • 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 registration
  • 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, CE/BZA may cause fetal harm when administered to a pregnant woman; 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 cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) and uridine 5'-diphospho-glucuronosyltransferase (UGT) are ineligible; the wash out period for such drugs is a minimum of 7 days or 5 half-lives
  • 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

Locations

  • University of Southern California not yet accepting patients
    Los Angeles, California, 90089, USA
  • Cancer Research Collaboration, Inc. not yet accepting patients
    Santa Ana, California, 92705, USA

Details

Status
accepting new patients
Start Date
Sponsor
Northwestern University
ID
NCT02694809
Phase
Phase 2
Study Type
Interventional
Last Updated
January 2017
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