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

A Randomized, Phase III Trial of Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions in Older Women With Early-Stage Breast Cancer (POWER II)

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).

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer Female
• Intervention / Treatment: Drug: Tamoxifen, Letrozole, Anastrozole, or Exemestane

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.

• Study Type: Interventional
• Enrollment (Estimated): 354
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Meagan Miller; Phone Number: 434-243-8101; Email: aey8fc@uvahealth.org

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Recruiting
      • Yale University
      • Contact: Cameron Groshek; Phone Number: 8604161250; Email: cameron.groshek@yale.edu
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia
      • Contact: Meagan Miller; Phone Number: (434) 243-8101; Email: aey8fc@uvahealth.org
    • Culpeper, Virginia, United States, 22701
      • Recruiting
      • University of Virginia Community Health
      • Contact: Ali Mahjoub; Email: AM3CG@uvahealth.org
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • INOVA Schar Cancer
      • Contact: Shawna Willey; Phone Number: 5714724724
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University
      • Contact: Deja Wortham; Email: worthamdn@vcu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria (summary):

• 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 Tamoxifen 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Arm; 90 days of pre-ET (endocrine therapy - tamoxifen or aromatase inhibitor) before Breast Cancer Surgery	Drug: Tamoxifen, Letrozole, Anastrozole, or Exemestane; Choice and dose of neoadjuvant endocrine therapy at the discretion of the treating medical oncologist.; Other Names: Endocrine Therapy
No Intervention: Control Arm; Will proceed directly to Breast Cancer Surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants who omit Radiation Therapy (RT) and are non-adherent to Endocrine Therapy (ET)	Proportion of participants who omit RT and are non-adherent to ET as measure through the 24-month adjuvant follow-up visit	24 months
Proportion of participants who are treated with Breast Cancer Surgery (BCS) + RT + AET	Proportion of participants who are treated with BCS + RT + AET as measured through the 24-month adjuvant follow-up visit	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment with pre-ET and its impact on Decision Conflict	Using Patient Reported Outcomes (PRO) assessments of Decisional Conflict Scale (DCS) to determine whether treatment with pre-ET lessens Decision Conflict. The DCS is a validated measure of patient perceptions of uncertainty surrounding treatment choices. The minimum score is a 0, which is interpreted as no decisional conflict, and the maximum score is 64, which is interpreted as the highest decisional conflict.	24 months
Treatment with pre-ET and its impact on Decision Regret	Using Patient Reported Outcomes (PRO) assessments of Decision Regret Scale (DRS) to determine whether treatment with pre-ET lessens Decision Regret. The DRS is a validated, 5-item scale that measures self-reported regret after health care decisions. DRS scores range from 0 (no regret) to 100 (high regret).	24 months
Assessing whether patient's final treatment correlates with their beliefs about breast cancer	Using the PRO assessment "Beliefs about Illness Questionnaire (BIP-Q)" to determine patient's beliefs about breast cancer. The BIP-Q is a validated survey to assess cognitive and emotional perceptions of illness.	7 months
Assessing whether patient's final treatment correlates with their beliefs about breast cancer	Using the PRO assessment "Beliefs about Medicine Questionnaire (BMQ)" to determine patient's beliefs about breast cancer. The BMQ is a validated survey designed to capture patients' perceptions about medicines and medicine adherence.	7 months
Assessing whether patient's final treatment correlates with their beliefs about breast cancer	Using the PRO assessment "Perceived Sensitivity to Medicine (PSM)" to determine patient's beliefs about breast cancer. The PSM is a validated 5-question survey designed to capture patients' opinions regarding their sensitivity to medications.	7 months
Assessing whether treatment with pre-ET leads to improved Health Related Quality of Life compared to those treated with standard of care	Using PRO Assessments: EORTC Quality of Life questionnaires (QLQ-C30) to determine whether treatment with pre-ET leads to improved health-related quality of life compared to those treated with standard of care	24 months
Assessing whether early side effects of ET correlate with patient treatment group within study arms	Using the PRO Assessment "Breast Cancer Prevention Trial Symptom Checklist (BCPT-SCL)" to assess whether early side effects of ET correlate with patient treatment group within study arms	24 months
Assessing whether early side effects of ET correlate with patient treatment group within study arms	Using the PRO Assessment "Center for Epidemiologic Study Depression Scale Revised (CESD-R)" to assess whether early side effects of ET correlate with patient treatment group within study arms	24 months
To obtain data on local recurrence	Local recurrence as measured through the 5 year adjuvant follow-up period	5 years
To obtain data on regional recurrence	Regional recurrence as measured through the 5 year adjuvant follow-up period	5 years
To obtain data on contralateral breast cancer	Contralateral breast cancer as measured through the 5 year adjuvant follow-up period	5 years
To obtain data on distant metastases	Distant metastases as measured through the 5 year adjuvant follow-up period	5 years
To obtain data on disease free survival	Disease free survival (DFS) as measured through the 5 year adjuvant follow-up period	5 years
To obtain data on cancer specific survival	Cancer specific survival as measured through the 5 year adjuvant follow-up period	5 years
To obtain data on overall survival	Overall survival (OS) as measured through the 5 year adjuvant follow-up period	5 years

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Shayna L Showalter, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2024
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): March 1, 2034

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: July 12, 2024
• First Posted (Actual): July 18, 2024

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; radiation; tamoxifen; geriatric; anastrozole; questionnaire; survey; letrozole; endocrine therapy; exemestane
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Benzene Derivatives; Nitriles; Triazoles; Stilbenes; Benzylidene Compounds; Letrozole; Anastrozole; Tamoxifen; exemestane
• Other Study ID Numbers: HSR230513

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No