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

NCT04568616 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: D20148NCI-2022-02378
• Study Type: interventional
• Target: 178
• Locations: 1 country
• Sites: 2

Brief Summary

This is a single-arm, open-label study testing the effects of neoadjuvant therapy with the aromatase inhibitor letrozole in post-menopausal women with Stage I-III ER+, HER2- breast cancer. Eligible subjects will be treated with letrozole therapy for 4 to 24 weeks prior to surgical resection of the tumor. Tumor specimens obtained at baseline (diagnostic biopsy) and at surgery (surgical specimen) will be compared using molecular analyses. A subset of subjects will be asked to provide an optional research tumor biopsy prior to treatment for molecular analysis. Subjects will be evaluated for treatment adherence and provide feedback via survey questionnaires to identify potential causes of non-adherence.

Conditions

Breast Cancer; ER Positive Breast Cancer

Keywords

Letrozole; Aromatase Inhibitor

Outcome Measures

Primary Outcomes (3)

• Change in Tumor CPT1-alpha levels

  Determine whether residual cancer cells exhibit upregulation of the fatty acid transport CPT1-alpha (compared to baseline) following neoadjuvant endocrine therapy in patients with ER+ breast cancer.

  Baseline to 4-12 Weeks

• Determine subject adherence to endocrine therapy as measured via urine analysis

  Urine analysis for drug metabolites will be used to determine subject adherence to endocrine therapy at three time points. (Protocol section 6.16.e) The outcome measure is percent of participants with adherence vs non-adherence as measured by urine samples tested for metabolites of adjuvant endocrine agents: tamoxifen, letrozole, anastrozole or exemestane. Urine tests will be recorded as positive or negative. Positive urine test = adherence.

  Before surgery (within 14 days before surgery, or on day of surgery); approximately 1 year after surgery; and approximately 3 years after surgery

• Treatment Satisfaction Questionnaire for Medication (TSQM) side effects score

  The Treatment Satisfaction Questionnaire for Medication (TSQM) v1.4 assesses subjects' satisfaction with their breast cancer medication over the past 2-3 weeks, or since last use. A modified 12-item questionnaire will address 4 domains: effectiveness (Item 1), side effects (Items 2-6), convenience (Items 7-9), and global satisfaction (Items 10-12). Item 2 (experience of side effects; yes/no) will be evaluated independently. Subjects will be dichotomized at the median score for analysis.

  Before surgery (approximately 4-24 weeks after the start of letrozole treatment), 1 year after surgery, and 3 years after surgery

Secondary Outcomes (8)

• Longest dimension(s) of primary tumor(s) pre- and post-treatment

  Baseline and after approximately 4 to 24 weeks of treatment

• Altered mitochondrial and fatty acid metabolism in surgical tissue specimen as compared to baseline tissue specimen.

  Baseline and at surgery (after approximately 4 to 24 weeks of treatment)

• Brief Pain Inventory (BPI) scores

  Baseline (within 28 days prior to start of letrozole), Before surgery (approximately 4-24 weeks after the start of letrozole treatment), 1 year after surgery, and 3 years after surgery

• Functional Assessment of Cancer Therapy- Endocrine Symptoms (FACT-ES) scores

  Baseline (within 28 days prior to start of letrozole), Before surgery (approximately 4-24 weeks after the start of letrozole treatment), 1 year after surgery, and 3 years after surgery

• Beliefs about Medication Questionnaire (BMQ) score

  Baseline (within 28 days prior to start of letrozole), Before surgery (approximately 4-24 weeks after the start of letrozole treatment), 1 year after surgery, and 3 years after surgery

Other Outcomes (3)

• Changes in residual cancer fatty acid.

  Baseline to 4 -12 weeks

• Changes in tumor cell type

  Baseline to 4 -12 weeks

• Relationship between duration of endocrine therapy and changes in tumor markers.

  Baseline to 4 -12 weeks

Study Arms (1)

Treatment

EXPERIMENTAL

Letrozole 2.5mg tablet administered once daily for 4 to \~12 weeks (window of + 4 weeks for surgical scheduling flexibility) final dose taken the day of surgery.

Drug: Letrozole 2.5mg

Interventions

Letrozole 2.5mg DRUG

Aromatase Inhibitor

Also known as: Femara

Treatment

Eligibility Criteria

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

You may qualify if:

• 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).
• The invasive cancer must be estrogen receptor alpha (ER)-positive, with ER staining present in greater than 50% of invasive cancer cells by IHC.
• 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 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.
• 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.
• 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.
• 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 neoadjuvant therapy for breast cancer. Bisphosphonate or denosumab treatment for metabolic bone issues are allowed.
• Women who are pregnant or lactating.

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (2)

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Letrozole

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Mary D Chamberlin, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: Patients receive letrozole orally (PO) once daily (QD) for 4-16 weeks up to the day of surgery in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. After surgery, a subset of patients start a hormone therapy (letrozole, anastrozole, or tamoxifen) and remain in the study for up to 3.5 years.

Study Record Dates

• First Submitted: September 22, 2020
• First Posted: September 29, 2020
• Study Start: August 13, 2021
• Primary Completion: April 2, 2025
• Study Completion (Estimated): August 13, 2029
• Last Updated: January 20, 2026

Record last verified: 2026-01

Locations

US (2)