Neoadjuvant therapy with letrozole for ER+ breast cancer

Phase II Study of Neoadjuvant ArOMatase Inhibitor Therapy for ER+ Breast Cancer (NAOMI)

This study is testing whether giving the medication letrozole to post-menopausal women with early-stage ER+ breast cancer before surgery can help shrink tumors and improve treatment outcomes.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 137 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Dartmouth-Hitchcock Medical Center (Academic / other)
• Drugs / interventions: denosumab
• Locations: 2 sites (Lebanon, New Hampshire and 1 other locations)
• Trial ID: NCT04568616 on ClinicalTrials.gov

What this trial studies

This study evaluates the effects of neoadjuvant therapy using the aromatase inhibitor letrozole in post-menopausal women diagnosed with Stage I-III ER+, HER2- breast cancer. Participants will receive letrozole treatment for a duration of 4 to 24 weeks before undergoing surgical tumor resection. The study aims to compare tumor specimens obtained before and after treatment through molecular analyses, while also assessing treatment adherence and gathering feedback from participants via surveys. This approach seeks to improve early intervention strategies for preventing cancer recurrence.

Who should consider this trial

Good fit: Ideal candidates include post-menopausal women with Stage I-III ER+, HER2- breast cancer who are planning to undergo surgical resection.

Not a fit: Patients with HER2-positive breast cancer or those with non-invasive breast cancer will not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly reduce the risk of cancer recurrence in patients with ER+ breast cancer.

How similar studies have performed: Other studies have shown promise with similar neoadjuvant approaches using aromatase inhibitors in ER+ breast cancer, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Histologic documentation of invasive breast cancer by core needle or incisional biopsy. Subjects without excess baseline tumor tissue are eligible and evaluable for Primary Objective #2 (re: adherence). Excess baseline biopsy tumor tissue sufficient to make ten 5- micron sections must be available for research use for a subject to be evaluable for Primary Objective #1 (re: molecular analyses).
2. The invasive cancer must be estrogen receptor alpha (ER)-positive, with ER staining present in greater than 50% of invasive cancer cells by IHC.
3. 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).
4. Clinical Stage I-III invasive breast cancer with the intent to treat with surgical resection of the primary tumor. Baseline tumor must be ≥0.5 cm. For the optional research biopsy (from 5 subjects), tumor must be

   ≥1 cm.
5. Patients with multicentric or bilateral disease are eligible if the subject is a candidate for clinically indicated neoadjuvant endocrine therapy. Samples from all available tumors are requested for research purposes.
6. Women over 18 years of age, for whom (A) neoadjuvant treatment with an aromatase inhibitor would be clinically indicated, and (B) adjuvant treatment with one of the following would be clinically indicated: tamoxifen; anastrozole; letrozole. Women must be postmenopausal, defined as last menstrual period \>2 years prior to registration, or \>1 yearer prior to registration with FSH and estradiol in post-menopausal range.
7. 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.
8. Ability to give informed consent.

Exclusion Criteria:

1. Prior endocrine therapy for any histologically-confirmed cancer or prevention of breast cancer in the last 10 years is not allowed.
2. Any other neoadjuvant therapy for breast cancer. Bisphosphonate or denosumab treatment for metabolic bone issues are allowed.
3. Women who are pregnant or lactating.

Where this trial is running

Lebanon, New Hampshire and 1 other locations

• Dartmouth Hitchcock Medical Center — Lebanon, New Hampshire, United States (Recruiting)
• Dartmouth-Hitchcock Medical Center — Lebanon, New Hampshire, United States (Recruiting)

Study contacts

• Principal investigator: Mary D Chamberlin, MD — Dartmouth-Hitchcock Medical Center
• Study coordinator: Research Nurse

Conditions Breast Cancer; ER Positive Breast Cancer; Letrozole; Aromatase Inhibitor