The PROMISE Study: Duavee in Women With DCIS

NCT02694809 | Completed Phase 2 DMC

• 4 other identifiers: NU 15B06STU00202100P30CA060553NCI-2016-00066
• Study Type: interventional
• Target: 142
• Locations: 1 country
• Sites: 10

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.

Conditions

Ductal Breast Carcinoma In Situ; Postmenopausal

Outcome Measures

Primary Outcomes (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.

  Up to 5 weeks

Secondary Outcomes (9)

• Expression of ERα

  Up to 5 weeks

• Expression of progesterone receptor (PR)

  Up to 5 weeks

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

  Up to 5 weeks

• Epithelial markers of progression

  Up to 5 weeks

• Expression of the stromal marker CD36

  Up to 5 weeks

Other Outcomes (8)

• Expression of estrogen-modulated genes in breast epithelium

  Up to 5 weeks

• Novel ER dependent-gene signatures in breast epithelium

  Up to 5 weeks

• Anterior Gradient 2 (AGR2)

  Up to 5 weeks

Study Arms (2)

Arm I (conjugated estrogens/bazedoxifene)

EXPERIMENTAL

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.

Drug: Conjugated Estrogens/Bazedoxifene; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm II (placebo)

PLACEBO COMPARATOR

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

Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Other: Placebo; Procedure: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Conjugated Estrogens/Bazedoxifene DRUG

Given PO

Arm I (conjugated estrogens/bazedoxifene)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (conjugated estrogens/bazedoxifene); Arm II (placebo)

Pharmacological Study OTHER

Correlative studies

Arm I (conjugated estrogens/bazedoxifene); Arm II (placebo)

Placebo OTHER

Given PO

Also known as: placebo therapy, PLCB, sham therapy

Arm II (placebo)

Quality-of-Life Assessment PROCEDURE

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (conjugated estrogens/bazedoxifene); Arm II (placebo)

Questionnaire Administration OTHER

Ancillary studies

Arm I (conjugated estrogens/bazedoxifene); Arm II (placebo)

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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)
• × institutional upper limit of normal Serum Creatinine OR Creatinine Clearance
• 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

You may not qualify 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 ≥ 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.
• 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.

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator
• Pfizer: collaborator
• University of Chicago - Department for Cancer Research: collaborator
• University of California, San Francisco: collaborator

Study Sites (10)

University of Colorado at Denver/ Department of Surgery

Aurora, Colorado, 80045, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

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

Geneva, Illinois, 60134, United States

Location

Northwestern University

Lake Forest, Illinois, 60045, United States

Location

John's Hopkins University

Baltimore, Maryland, 21287, United States

Location

Dana Farber/Partners Cancer Care Inc

Boston, Massachusetts, 02115, United States

Location

Washington University in St. Louis/ Siteman Cancer Center

St Louis, Missouri, 63110, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburg/ Magee-Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

Estrogens, Conjugated (USP); bazedoxifene

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Swati Kulkarni, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2016
• First Posted: March 1, 2016
• Study Start: January 1, 2017
• Primary Completion: June 19, 2024
• Study Completion: June 19, 2024
• Last Updated: January 28, 2025

Record last verified: 2025-01

Locations

US (10)