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History of Changes for Study: NCT02694809
Conjugated Estrogens/Bazedoxifene in Treating Patients With Ductal Carcinoma in Situ Undergoing Surgery
Latest version (submitted May 27, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 February 24, 2016 None (earliest Version on record)
2 September 1, 2016 Study Status
3 January 3, 2017 Recruitment Status, Study Status and Contacts/Locations
4 January 8, 2018 Study Status
5 March 2, 2018 Study Status and Contacts/Locations
6 May 24, 2018 Study Status and Contacts/Locations
7 June 18, 2018 Outcome Measures, Study Design, Study Status, Contacts/Locations, Arms and Interventions, Eligibility, Study Description and Study Identification
8 June 21, 2018 Eligibility, Study Design, Study Status and Study Identification
9 June 27, 2018 Contacts/Locations and Study Status
10 August 15, 2018 Contacts/Locations and Study Status
11 February 15, 2019 Contacts/Locations, Study Status, Eligibility, Study Design, Study Description and Sponsor/Collaborators
12 April 17, 2019 Study Status
13 May 22, 2019 Study Status and Contacts/Locations
14 June 10, 2019 Study Status and Eligibility
15 June 12, 2019 Sponsor/Collaborators and Study Status
16 December 11, 2019 Study Status and Contacts/Locations
17 April 30, 2021 Study Status
18 May 27, 2021 Contacts/Locations, Study Status and Eligibility
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Study NCT02694809
Submitted Date:  February 24, 2016 (v1)

Open or close this module Study Identification
Unique Protocol ID: NU 15B06
Brief Title: Conjugated Estrogens/Bazedoxifene in Treating Patients With Ductal Carcinoma in Situ Undergoing Surgery
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)
Secondary IDs: STU00202100
NU 15B06 [Northwestern University]
P30CA060553 [U.S. NIH Grant/Contract]
NCI-2016-00066 [Registry Identifier: CTRP (Clinical Trial Reporting Program)]
Open or close this module Study Status
Record Verification: February 2016
Overall Status: Not yet recruiting
Study Start: March 2016
Primary Completion: September 2019 [Anticipated]
Study Completion:
First Submitted: February 24, 2016
First Submitted that
Met QC Criteria:
February 24, 2016
First Posted: March 1, 2016 [Estimate]
Last Update Submitted that
Met QC Criteria:
February 24, 2016
Last Update Posted: March 1, 2016 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Northwestern University
Responsible Party: Sponsor
Collaborators: Pfizer
National Cancer Institute (NCI)
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: Yes
Open or close this module Study Description
Brief 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.
Detailed Description:

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.

Open or close this module Conditions
Conditions: Ductal Breast Carcinoma In Situ
Postmenopausal
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Parallel Assignment
Number of Arms: 2
Masking: Double (Participant, Investigator)
Allocation: Randomized
Enrollment: 130 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Arm I (conjugated estrogens/bazedoxifene)
Patients receive conjugated estrogens/bazedoxifene PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Drug: Conjugated Estrogens/Bazedoxifene
Given PO
Cytology Specimen Collection Procedure
Correlative studies
Other Names:
  • Cytologic Sampling
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Procedure: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Questionnaire Administration
Ancillary studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD on days 1-28 in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Cytology Specimen Collection Procedure
Correlative studies
Other Names:
  • Cytologic Sampling
Laboratory Biomarker Analysis
Correlative studies
Pharmacological Study
Correlative studies
Placebo
Given PO
Other Names:
  • placebo therapy
  • PLCB
  • sham therapy
Procedure: Quality-of-Life Assessment
Ancillary studies
Other Names:
  • Quality of Life Assessment
Questionnaire Administration
Ancillary studies
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Change in Ki-67 protein expression
[ Time Frame: Baseline to 4 weeks ]

Evaluating if CE/BZA reduces proliferation as measured by Ki-67 protein expression. Change in Ki-67 between baseline and end of the intervention (4 weeks) will be measured.
Secondary Outcome Measures:
1. Change in ARCS signature
[ Time Frame: Baseline to 4 weeks ]

To assess whether CE/BZA alters markers associated with progression to invasive cancer (ARCS signature) in postmenopausal women with DCIS compared to placebo.
2. Change in QOL using MENQOL questionnaire
[ Time Frame: Baseline to 4 weeks ]

The difference in the MENQOL answers between baseline and end of the intervention will be evaluated.
Other Outcome Measures:
1. Change in CD36
[ Time Frame: Baseline to 4 weeks ]

Changes in the stromal marker CD36 between baseline and the end of the intervention will be assessed in women with DCIS treated with CE/BZA compared to placebo.
2. Change in hormone receptor (ERa and PR) expression
[ Time Frame: Baseline to 4 weeks ]

To assess changes in hormone receptor (ERα and PR) expression in women with DCIS treated with CE/BZA compared to placebo.
3. Changes in global gene expression profiling using RNA sequencing
[ Time Frame: Baseline to 4 weeks ]

Using RNA sequencing to assess changes in global gene expression profiling in women with DCIS treated with CE/BZA when compared to placebo.
4. Identify possible polymorphisms
[ Time Frame: Up to 4 weeks before surgery ]

Peripheral blood will be collected at the baseline visit (preferably) or any time before surgery to identify possible polymorphisms that may affect the metabolism of CE/BZA.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 75 Years
Sex: Female
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • 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

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 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
Open or close this module Contacts/Locations
Study Officials: Swati Kulkarni, MD
Principal Investigator
Northwestern University
Locations: United States, California
University of Southern California
Los Angeles, California, United States, 90089-9235
Contact:Contact: Julie E. Lang, MD, FACS 323-442-6868
University of California
San Francisco, California, United States, 94143-0511
Contact:Contact: Thea Tlsty, PhD 415-502-6115
Cancer Research Collaboration, Inc.
Santa Ana, California, United States, 92705
Contact:Contact: Nimmi Kapoor, MD 714-541-0101
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Contact:Contact: Swati A. Kulkarni 312-503-2899 skulkarn@nm.org
Contact:Principal Investigator: Swati A. Kulkarni, MD
Contact:Sub-Investigator: Seema Khan, MD
Contact:Sub-Investigator: Luis S. Blanco Jr., MD
University of Chicago
Chicago, Illinois, United States, 60637
Contact:Contact: Geoffrey Greene, PhD 773-702-6964
University of Chicago
Chicago, Illinois, United States, 60637
Contact:Contact: Nora Jaskowiak, M.D., FACS 773-702-2048
Northwestern University
Lake Forest, Illinois, United States, 60045
Contact:Contact: Tara M. Breslin, MD, FACS tbreslin@nm.org
United States, Maryland
John's Hopkins University
Baltimore, Maryland, United States, 21287
Contact:Contact: David M. Euhus, MD 410-502-0197
United States, Massachusetts
Dana Farber/Partners Cancer Care Inc
Boston, Massachusetts, United States, 02115
Contact:Contact: Tari A. King, MD 617-632-3891
Dana Farber/Partners Cancer Care Inc
Boston, Massachusetts, United States, 02115
Contact:Contact: Judy E. Garber, MD, MPH 617-632-5961
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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