Pre-Operative Window of ET to Inform RT Decisions (POWER II)

NCT ID: NCT06507618

Last Updated: 2025-09-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 354 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-07-19
• Study Completion Date: 2034-03-01

Brief Summary

This is a Phase III, multisite exploratory study for women ≥ 65 years of age with early stage estrogen receptor positive (ER+) breast cancer. These individuals will be treated randomly assigned to one of two groups:

Intervention, treated with 3 months of pre-operative endocrine therapy (pre-ET) OR Control, participants follow standard of care and proceed directly to breast cancer surgery.

Both arms will be assessed for tolerance and compliance to the endocrine therapy by patient reported outcome (PRO) measures (patient surveys).

Detailed Description

Early-stage, estrogen receptor positive (ER+) breast cancer is traditionally treated with breast conserving surgery (BCS), radiation therapy (RT) and 5-10 years of adjuvant endocrine therapy (AET). Radiation therapy (RT) omission is an established treatment paradigm for women 65 years and older with ER+, node negative, small (≤ 3 cm) breast cancer. Despite the option for RT omission being recommended in the National Comprehensive Cancer Network (NCCN) guidelines, multiple modern studies demonstrate that a majority of older women still receive RT, raising concern for over-treatment. Conversely, there are a portion of patients who choose to omit RT but are not able to tolerate AET and thus are at risk for under-treatment and worse oncologic outcomes.

In the POWER I trial, patients were treated with 90 days of pre-operative endocrine therapy (pre-ET) as a window to establish endocrine therapy (ET) tolerance. The POWER I trial prospectively validated 90 days of pre-operative ET to determine if it could be used as a tool to inform adjuvant RT decisions and recommendations by patients and physicians respectively. Ninety days of pre-ET was shown to influence patient and physician preferences regarding adjuvant RT.

In the POWER II trial, participants will be randomized to treatment on either a) an intervention arm consisting of a 90-day window of pre-ET or b) the standard of care (control) arm in which participants proceed directly to BCS. In both arms, the decision to omit or administer adjuvant RT will be made by the treating physicians and patients. While not required per protocol, all patients will be recommended for AET if deemed appropriate by their oncologist, and adherence through 2 years will be monitored. The POWER I study revealed that pre-ET impacts patients' and physicians' decisions regarding adjuvant therapy and facilitates adjuvant therapy decisions that meld patient preferences and side effect tolerance. The purpose of the POWER II study is to examine whether 90 days of pre-ET results in a decrease in the number of (1) patients being treated with BCS alone and (2) patients treated with BCS+RT+AET. Adherence to AET will be defined as taking AET at 2 years post-BCS.

Conditions

Breast Cancer Female

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention Arm

90 days of pre-ET (endocrine therapy - tamoxifen or aromatase inhibitor) before Breast Cancer Surgery

Group Type: EXPERIMENTAL

Tamoxifen, Letrozole, Anastrozole, or Exemestane

Intervention Type: DRUG

Choice and dose of neoadjuvant endocrine therapy at the discretion of the treating medical oncologist.

Control Arm

Will proceed directly to Breast Cancer Surgery

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Tamoxifen, Letrozole, Anastrozole, or Exemestane

Choice and dose of neoadjuvant endocrine therapy at the discretion of the treating medical oncologist.

Intervention Type: DRUG

Other Intervention Names

Endocrine Therapy

Eligibility Criteria

Inclusion Criteria

• Diagnosis of ER+, PR +/-, and HER2- non amplified invasive breast cancer and clinically negative nodes
• ECOG performance status 0-2
• Females, aged ≥ 65 years
• Patient is eligible for BCS and opted for BCS
• Patient is a candidate for radiation therapy
• Patient is a candidate for endocrine therapy (tamoxifen or an aromatase inhibitor)
• Ability to take oral medication and be willing to adhere to endocrine therapy for the 3-month period prior to BCS
• Agreement to adhere to Lifestyle Considerations (details in protocol) throughout study duration
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

• Bilateral synchronous breast cancer
• Multicentric disease
• Prior use of SERMS or aromatase inhibitors
• History of ipsilateral breast radiation therapy
• Has a known additional malignancy that is progressing and/or requires active treatment with cytotoxic chemotherapy or radiation therapy. Malignancies deemed stable and low risk for complication per investigator's judgment may be allowed after discussion with multi-site PI.
• Current or planned use of a strong CYP2D6 inhibitor (e.g., Fluvoxamine, Paroxetine) and is not able to receive an endocrine therapy agent that does not use the CYP2D6 pathway.

• Minimum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Shayna Showalter, MD

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Shayna L Showalter, MD

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

INOVA Schar Cancer

Fairfax, Virginia, United States

Site Status: RECRUITING

Virginia Commonwealth University

Richmond, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Meagan Miller

Role: CONTACT

aey8fc@uvahealth.org

434-243-8101

Facility Contacts

Meagan Miller

Role: primary

aey8fc@uvahealth.org

(434) 243-8101

Shawna Willey

Role: primary

5714724724

Deja Wortham

Role: primary

worthamdn@vcu.edu

Other Identifiers

HSR230513

Identifier Type: -

Identifier Source: org_study_id