Clinical trial NCT06507618: Pre-Operative Window of ET to Inform RT Decisions (POWER II)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer Female
Keywords: breast cancer
endocrine therapy
radiation
letrozole
anastrozole
exemestane
tamoxifen
survey
questionnaire
geriatric
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2024-07-18
Enrollment: 354
Sex: FEMALE
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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 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.

Primary outcomes:
measure: Proportion of participants who omit Radiation Therapy (RT) and are non-adherent to Endocrine Therapy (ET)
timeFrame: 24 months
measure: Proportion of participants who are treated with Breast Cancer Surgery (BCS) + RT + AET
timeFrame: 24 months
Secondary outcomes:
measure: Treatment with pre-ET and its impact on Decision Conflict
timeFrame: 24 months
measure: Treatment with pre-ET and its impact on Decision Regret
timeFrame: 24 months
measure: Assessing whether patient's final treatment correlates with their beliefs about breast cancer
timeFrame: 7 months
measure: Assessing whether patient's final treatment correlates with their beliefs about breast cancer
timeFrame: 7 months
measure: Assessing whether patient's final treatment correlates with their beliefs about breast cancer
timeFrame: 7 months
measure: Assessing whether treatment with pre-ET leads to improved Health Related Quality of Life compared to those treated with standard of care
timeFrame: 24 months
measure: Assessing whether early side effects of ET correlate with patient treatment group within study arms
timeFrame: 24 months
measure: Assessing whether early side effects of ET correlate with patient treatment group within study arms
timeFrame: 24 months
measure: To obtain data on local recurrence
timeFrame: 5 years
measure: To obtain data on regional recurrence
timeFrame: 5 years
measure: To obtain data on contralateral breast cancer
timeFrame: 5 years
measure: To obtain data on distant metastases
timeFrame: 5 years
measure: To obtain data on disease free survival
timeFrame: 5 years
measure: To obtain data on cancer specific survival
timeFrame: 5 years
measure: To obtain data on overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
Study officials:
affiliation: University of Virginia
name: Shayna L Showalter, MD
role: PRINCIPAL_INVESTIGATOR
References: