Evaluating the Use of a Medication 'Switch' vs Guideline-directed Interventions for Relieving Side Effects of Aromatase Inhibitors Among Breast Cancer Patients

NCT07071038 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: Study0200199423KUH994NCI-2025-09080
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

Researchers have learned that about 50% of women do not finish the standard 5-year breast cancer treatment with an aromatase inhibitor. An aromatase inhibitor is hormone therapy that lowers the chance of breast cancer coming back (recurring) after surgery by blocking an enzyme in fat tissue called aromatase; aromatase changes other hormones in the body to estrogen. Women who do not complete the standard 5-year treatment are at higher risk of their cancer coming back. The goal of this research is to prevent breast cancer from coming back after surgery by helping women to stay on treatment with aromatase inhibitors. Researchers believe the best path to help women to stay on treatment is to create a better way to manage (control) side effects.

Conditions

Breast Cancer; Adjuvant Treatment; Early Stage Breast Cancer

Keywords

breast cancer surgery; aromatase inhibitor; aromatase side effects; hormone therapy; quality of life; adherence; early breast cancer; switching medications; hormonal therapy; letrozole; anastrozole; exemestane; tamoxifen; adjuvant therapy

Outcome Measures

Primary Outcomes (1)

• Change in Endocrine Symptom Burden at 3 months

  The primary outcome of this study is the change in the Functional Assessment of Cancer Therapy Endocrine Subscale (FACT-ES) endocrine symptom subscale (ESS-23) survey score as measured from the time of randomization to 3 months, or at the time of cross-over or discontinuation of AI due to intolerable side effects, whichever comes first. The ESS-23 score ranges from 0-92, with lower scores indicating higher symptom burden.

  3 months after randomization

Secondary Outcomes (8)

• Change in Symptom Burden at 3 and 6 months (FACT-ES)

  3 and 6 months after randomization

• Change in Symptom Burden at 3 and 6 months (PROMIS)

  3 and 6 months

• Change in Symptom Burden at 3 and 6 Months (FSFI)

  3 and 6 months

• Quality of life at 3 and 6 months

  3 and 6 months after randomization

• Adherence to Endocrine Therapy at 3 and 6 months

  3 and 6 months after randomization

Other Outcomes (3)

• TSQM Screening Tool

  2 years after enrollment

• Responder Thresholds to Define Clinically Meaningful Change in Symptoms

  3 and 6 months after randomization

• Disparities and Access to Care

  6 months after randomization

Study Arms (2)

Switch

ACTIVE COMPARATOR

Participants (people taking part in this study) enrolled to this study will receive treatment with the aromatase inhibitor (AI) Letrozole and fill out surveys to check for side effects to see how the side effects are making their daily life harder. If side effects are reported, the Participant will be randomized (placed by chance) to a group where they will receive either a different AI ('switch') or receive guideline directed intervention "GDI" using medication and non-medication treatment options.

Drug: Switch

Guideline Directed Intervention (GDI)

ACTIVE COMPARATOR

Participants will receive evidence-based (proven to work) treatment options for side effects according to national guidelines; these may include medications or non-medication options (guideline-directed interventions, GDIs).

Other: Guideline Directed Intervention (GDI)

Interventions

Switch DRUG

Participants in the switch arm will receive a new prescription for either anastrozole or exemestane at a dose of 1mg or 25mg daily, respectively. The choice of AI in the first line setting will be at the discretion of the treating oncologist. If side effects persist after the 1st line switch, the participant will have the option to switch to another AI not yet tried, or to tamoxifen at 20mg daily

Switch

Guideline Directed Intervention (GDI) OTHER

Subjects in this group will receive a guideline-directed intervention "GDI" using medication and/or non-medication treatment options according to the National Comprehensive Cancer Network (NCCN) supportive care guidelines. A GDI Book was created for this trial that lists treatment options and resources for each of the common side effects of hormonal therapy and is available for providers and staff to help select treatment options. For less common side effects with limited evidence-based options, treatment will be determined in collaboration with the treating provider and PI, using best available evidence.

Guideline Directed Intervention (GDI)

Eligibility Criteria

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

You may qualify if:

• Histologic documentation of DCIS or invasive breast cancer by core needle or incisional biopsy.
• The DCIS or invasive cancer must be estrogen receptor alpha (ER)-positive
• The invasive cancer must be HER2-negative (IHC 0-1+, or with a FISH ratio of \<1.8 if IHC is 2+ or if IHC has not been done)
• Clinical Stage I-III invasive breast cancer or DCIS
• Patients for whom adjuvant treatment with one of the following would be clinically indicated: letrozole, anastrozole, exemestane
• Patients who anticipate continuing with adjuvant endocrine therapy for a minimum of 2 years at the time of registration
• Women over 18 years of age who are post-menopausal, defined as last menstrual period \>2 years prior to registration, or \>1 year prior to registration with FSH and estradiol in post-menopausal range.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) \>1,000/mm3 and platelet count \> 75,000/mm3
• Total bilirubin \<1.5 x the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x ULN.
• Ability to give informed consent.

You may not qualify if:

• Prior endocrine therapy for any histologically-confirmed cancer or prevention of breast cancer in the last 10 years is not allowed.
• Any other adjuvant therapy for breast cancer. Exception: Bisphosphonate or denosumab treatment for metabolic bone issues are allowed.
• Patients who are prescribed tamoxifen as the first endocrine therapy rather than an aromatase inhibitor.
• Women who are pregnant or lactating.
• Prisoners.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Central Study Contacts

Kristina M. Willey

CONTACT

603-650-7705; Kristina.M.Willey@hitchcock.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is phase II, randomized-controlled trial with option for cross-over that compares the effectiveness of a 'switch' in hormonal therapy to guideline-directed intervention (GDI) for frontline management of side effects of aromatase inhibitors among breast cancer patients. After starting AI, participants will be contacted at 2 weeks, and then every 4-weeks to screen for development of bothersome side effects using a validated screening tool. Participants with a positive screen will receive standard of care advice for managing side effects, and in addition will be randomized 1:1 to either receiving a different AI ("switch") or GDI. In addition to baseline, surveys will be administered at time of positive screening (randomization), and 3- and 6-months.

Study Record Dates

• First Submitted: June 23, 2025
• First Posted: July 17, 2025
• Study Start: October 17, 2025
• Primary Completion (Estimated): August 5, 2026
• Study Completion (Estimated): August 5, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-01

Locations

US (1)