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Ductal Breast Carcinoma In SituPhase 2NCT02694809

The PROMISE Study: Duavee in Women With DCIS

A Phase 2 study testing Conjugated Estrogens/Bazedoxifene, Laboratory Biomarker Analysis and Pharmacological Study in people with Ductal Breast Carcinoma In Situ and Postmenopausal, run by Northwestern University at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 79 years, women only
What is being tested?
Conjugated Estrogens/Bazedoxifene, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
142 participants
Where
10 sitesUnited States
Study dates
Jan 2017to 19 Jun 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 79 years
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Women must have newly diagnosed histologically confirmed ER (+) 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 NU, our pathologists will review the slides to confirm the diagnosis.
  • Note: 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.
  • Note: Women presenting with bilaterial 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 outlined later in the protocol.
  • DCIS must be ≥ 1cm based on extent of calcifications, presence of a mass on ultrasound OR enhancement on MRI OR DCIS must be ≥ 5mm of DCIS on one single core. Can be < 5mm if DCIS is identified on multiple cores (at least 2 cores)
  • Women presenting after excision with positive margins are eligible. Ki-67, Cox-2, P-16, expression in immediately adjacent tissue is similar to what is found in DCIS.
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  • Note: Positive margins are defined as DCIS present at the inked margin or DCIS <1mm 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 postmenopausal status is required for these patients and will be measured by testing levels of estradiol, progesterone and 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.
  • Women in the age range of ≥18-79 (inclusive)
  • ECOG performance status ≤ 2 (Karnofsky ≥60%, see Appendix A).
  • Patients must have normal organ and marrow function as defined below Leukocytes ≥3,000/mcL Platelets ≥100,000/mcL Hemoglobin ≥ 9g/dl Total Bilirubin ≤ 1.5 x upper limit of normal (ULN) AST (SGOT) and ALT (SGPT)
  • 2.5 × institutional upper limit of normal Serum Creatinine OR Creatinine Clearance
  • 1.5 x ULN ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal (calculated with the Cockcroft-Gault Equation in EPIC)
  • Patients must have the ability to swallow oral medication
  • Ability to understand and the willingness to sign a written informed consent document and comply with all procedures

Who cannot join

  • 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 ≥ 1 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 HRT, 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 of invasive breast cancer Note: Patients who do not currently have a diagnosis of invasive breast cancer but who are planning to undergo additional standard of care testing to rule out a diagnosis of invasive breast cancer (such as future imaging or biopsy) are eligible. If the results of this standard of care testing later confirm that the subject has a diagnosis of invasive breast cancer, the subject should be withdrawn from the study at that time.
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  • Patients with recurrent ipsilateral DCIS
  • Any of the following conditions, or a known history of any of the following:
  • deep venous thrombosis,
  • pulmonary embolism,
  • retinal vascular thrombosis,
  • any arterial thrombosis,- Known protein C, protein S, or anti-thrombin deficiency or other known thrombophilic disorders including stroke and myocardial infarction
  • 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 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. Refer to Appendix C.
  • Note: As this list is constantly evolving, 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.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites

  • University of Colorado at Denver/ Department of Surgery

    Aurora, Colorado, 80045

  • John's Hopkins University

    Baltimore, Maryland, 21287

  • Dana Farber/Partners Cancer Care Inc

    Boston, Massachusetts, 02115

  • Northwestern University

    Chicago, Illinois, 60611

  • Northwestern Medicine - Delnor/Warrenville Cancer Centers/Central DuPage Hospital

    Geneva, Illinois, 60134

  • Northwestern University

    Lake Forest, Illinois, 60045

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburg/ Magee-Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

  • Washington University in St. Louis/ Siteman Cancer Center

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: A Large-scale Multicenter Phase II Study Evaluating the Protective Effect of a Tissue Selective Estrogen Complex (TSEC) in Women With Newly Diagnosed Ductal Carcinoma in Situ

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.

Read the detailed description

PRIMARY OBJECTIVES;

  • To determine if CE/BZA reduces proliferation as measured by Ki-67 protein expression

Secondary Objectives:

  • To determine if CE/BZA modulates expression of ERα, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2).
  • To determine if CE/BZA modulates a previously validated set of epithelial markers of progression.
  • To determine if TSECs will restore expression of the stromal marker CD36 and repress pro-tumorigenic ECM proteins and soluble factors.
  • 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.
  • 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

  • To determine if CE/BZA alters expression of estrogen-modulated genes and elicits novel ER dependent-gene signatures in breast epithelium
  • To demonstrate that CE/BZA does not upregulate Anterior Gradient 2 (AGR2), a marker of ERα agonist activity.
  • 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.
  • 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.
  • 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) for 28 +/- 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

ARM II: Patients receive placebo PO QD for 28 +/- 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.

Being tested
Conjugated Estrogens/Bazedoxifene, Laboratory Biomarker Analysis, Pharmacological Study, Placebo, Quality-of-Life Assessment
Medical subject headings
Carcinoma, Intraductal, Noninfiltrating

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Conjugated Estrogens/BazedoxifeneDrug

    Given PO

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • PlaceboOther

    Also called placebo therapy, PLCB, sham therapy

    Given PO

  • Quality-of-Life AssessmentProcedure or surgery

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT02694809
Study groupRoleWhat they receive
Arm I (conjugated estrogens/bazedoxifene)ExperimentalPatients receive conjugated estrogens/bazedoxifene orally (PO) once daily (QD) for 28 +/- 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Receives: Drug: Conjugated Estrogens/Bazedoxifene; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration
Arm II (placebo)Placebo comparatorPatients receive placebo PO QD for 28 +/- 7 days in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Ki-67 protein expression

    Evaluating if CE/BZA reduces proliferation as measured by Ki-67 protein expression. Change in Ki-67 between baseline and end of the intervention will be measured.

    Measured: Up to 5 weeks

Secondary outcomes (9)

  1. Expression of ERα

    Determine if CE/BZA modulates expression of ERα.

    Measured: Up to 5 weeks

  2. Expression of progesterone receptor (PR)

    Evaluate if CE/BZA modulates expression of PR

    Measured: Up to 5 weeks

  3. Expression of human epidermal growth factor receptor 2 (HER-2)

    Determine if CE/BZA modulates expression of HER-2.

    Measured: Up to 5 weeks

  4. Epithelial markers of progression

    Evaluate if CE/BZA modulates a previously validated set of epithelial markers of progression.

    Measured: Up to 5 weeks

  5. Expression of the stromal marker CD36

    Determine if TSECs will restore expression of the stromal marker CD36.

    Measured: Up to 5 weeks

  6. Repression of pro-tumorigenic ECM proteins

    Determine if TSECs will repress pro-tumorigenic ECM proteins.

    Measured: Up to 5 weeks

  7. Repression of soluble factors

    Determine if TSECs will repress soluble factors.

    Measured: Up to 5 weeks

  8. Quality of Life (QOL)

    Evaluate 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.

    Measured: Up to 5 weeks

  9. Breast Cancer Prevention Trial Eight Symptom Scale (BESS) questionnaire

    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.

    Measured: Up to 5 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2016 (estimated)
  2. Study startJan 2017
  3. Primary completion19 Jun 2024
  4. Study completion19 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
142 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02694809
Sponsor's protocol ID
NU 15B06
Other IDs
STU00202100, NU 15B06, P30CA060553, NCI-2016-00066
Status last verified
Jan 2025
First submitted
24 Feb 2016
Last updated
28 Jan 2025
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Conjugated Estrogens/Bazedoxifene, Laboratory Biomarker Analysis and Pharmacological Study in people with Ductal Breast Carcinoma In Situ and Postmenopausal, run by Northwestern University at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Ki-67 protein expression (time frame: Up to 5 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02694809.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2025.

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