- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04568616
Neoadjuvant ArOMatase Inhibitor Therapy for ER+ Breast Cancer (NAOMI) (NAOMI)
Phase II Study of Neoadjuvant ArOMatase Inhibitor Therapy for ER+ Breast Cancer (NAOMI)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Approximately 70% of breast cancers express estrogen receptor alpha (ER), which is activated by estrogens and typically drives cancer cell growth. Adjuvant therapy with anti-estrogens such as tamoxifen and aromatase inhibitors (AIs) is commonly used to inhibit ER to prevent cancer (re)growth after early-stage breast tumors are surgically removed. However, ~33% of such patients (~300,000 new cases per year worldwide) will eventually develop anti-estrogen-resistant breast cancer that is metastatic or locally advanced; at this stage, the disease is almost never cured using available therapies and is uniformly fatal. Therefore, more effective treatment early in the course of disease (i.e., in the adjuvant setting, shortly after surgical removal of a tumor) has huge potential to prevent cancer regrowth.
Most often, ER+ breast cancers re-emerge in the years after the end of the standard five-year anti-estrogen treatment regimen (called 'late recurrence'). Recent data indicate that continued anti-estrogen therapy in patients who remain "disease-free" after five years of anti-estrogen therapy modestly prevents cancer recurrence. However, tumor cells are detectable in bone marrow of patients who are "disease-free." Thus, anti-estrogen therapy in "disease-free" patients likely suppresses the growth of undetectable tumor cells, keeping them in a "clinically dormant" state (i.e., undetectable by standard clinical methods). Little is known about how such dormant cancer cells survive. This clinical study will help identify the signaling pathways essential for the survival of clinically dormant ER+ breast cancer cells to enable the development of more effective therapies to eradicate such cells and prevent cancer recurrence.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Research Nurse
- Phone Number: 1-800-639-6918
- Email: Cancer.Research.Nurse@dartmouth.edu
Study Locations
-
-
New Hampshire
-
Lebanon, New Hampshire, United States, 03756
- Recruiting
- Dartmouth-Hitchcock Medical Center
-
Contact:
- Research Nurse, RN
- Phone Number: 800-639-6918
- Email: Cancer.Research.Nurse@Dartmouth.edu
-
Principal Investigator:
- Mary D Chamberlin, MD
-
Lebanon, New Hampshire, United States, 03756
- Not yet recruiting
- Dartmouth Hitchcock Medical Center
-
Contact:
- Mary D Chamberlin, MD
- Phone Number: 800-639-6918
- Email: mary.d.chamberlin@hitchcock.org
-
Contact:
- Research Nurse
- Phone Number: 800-639-6918
- Email: cancer.research.nurse@dartmouth.edu
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Histologic documentation of invasive breast cancer by core needle or incisional biopsy. Excess baseline biopsy tumor tissue sufficient to make ten 5-micron sections must be available for research use as part of this study.
- 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 ≥1 cm to provide adequate tissue.
- 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 neoadjuvant treatment with an aromatase inhibitor would be clinically indicated. Women must be surgically, medically, or naturally post-menopausal.
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.
Exclusion Criteria:
- Prior endocrine therapy for any histologically-confirmed cancer is not allowed. Prior endocrine therapy that was administered ≥5 years ago for the prevention of breast cancer in patients with no history of breast cancer is allowed.
- Any other neoadjuvant therapy for breast cancer. Bisphosphonate treatment for bone symptoms is allowed.
- Women who are pregnant or lactating.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment
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.
|
Aromatase Inhibitor
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Tumor CPT1-alpha levels
Time Frame: Baseline to 4-12 Weeks
|
Determine whether residual cancer cells exhibit upregulation of the fatty acid transport CPT1-alpha (compared to baseline)
|
Baseline to 4-12 Weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of subjects who experience Clinical Response
Time Frame: 4 to12 Weeks
|
Determine the proportion of subjects who experience clinical response, defined as a ≥50% decrease in the longest dimension of the primary tumor.
The longest dimension(s) of the primary tumor(s) will be measured from radiological images acquired as per standard of care before (up to 4 wk prior to) neoadjuvant letrozole treatment, and after neoadjuvant letrozole treatment (prior to surgery).
If multiple primary tumors are detected, the sum of the longest diameters will be used to provide a single measurement at each time point for each subject.
Pre- and post-treatment tumor lengths will be compared.
|
4 to12 Weeks
|
Change in tumor CPT1-alpha histoscore
Time Frame: Baseline to 4 -12 weeks
|
Determine whether residual cancer cells exhibit altered levels of CPT1-alpha compared to baseline tumors.
Specimens will be immunofluorescently stained using an antibody against CPT1-alpha.
CPT1-alpha histoscore levels will be measured using Halo software to determine whether post-neoadjuvant therapy cancer cells exhibit increased levels compared to baseline cancer cells.
|
Baseline to 4 -12 weeks
|
Change in tumor mitochondrial content per cell
Time Frame: Baseline to 4 -12 weeks
|
Determine whether residual cancer cells exhibit altered mitochondrial length compared to baseline tumors.
Specimens will be immunofluorescently stained using an antibody against TOM20.
TOM20-stained organelle length per cell will be measured using Halo software to determine whether post-neoadjuvant therapy cancer cells exhibit increased mitochondrial content compared to baseline cancer cells.
|
Baseline to 4 -12 weeks
|
Change in tumor ACC histoscore
Time Frame: Baseline to 4 -12 weeks
|
Determine whether residual cancer cells exhibit altered levels of ACC compared to baseline tumors.
Specimens will be immunofluorescently stained using an antibody against ACC.
ACC levels will be measured using Halo software to determine whether post-neoadjuvant therapy cancer cells exhibit increased levels compared to baseline cancer cells.
|
Baseline to 4 -12 weeks
|
Change in tumor FASN histoscore
Time Frame: Baseline to 4 -12 weeks
|
Determine whether residual cancer cells exhibit altered levels of FASN compared to baseline tumors.
Specimens will be immunofluorescently stained using an antibody against FASN.
FASN levels will be measured using Halo software to determine whether post-neoadjuvant therapy cancer cells exhibit increased levels compared to baseline cancer cells.
|
Baseline to 4 -12 weeks
|
Change in tumor CD36 histoscore
Time Frame: Baseline to 4 -12 weeks
|
Determine whether residual cancer cells exhibit altered levels of CD36 compared to baseline tumors.
Specimens will be immunofluorescently stained using an antibody against CD36.
CD36 levels will be measured using Halo software to determine whether post-neoadjuvant therapy cancer cells exhibit increased levels compared to baseline cancer cells.
|
Baseline to 4 -12 weeks
|
Change in tumor lipid droplet content per cell
Time Frame: Baseline to 4 -12 weeks
|
Determine whether residual cancer cells exhibit altered lipid droplet content compared to baseline tumors.
Specimens will be immunofluorescently stained using an antibody against perilipin.
Perilipin-stained organelle content per cell will be measured using Halo software to determine whether post-neoadjuvant therapy cancer cells exhibit increased lipid droplet content compared to baseline cancer cells.
|
Baseline to 4 -12 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Mary D Chamberlin, MD, Dartmouth-Hitchcock Medical Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hormone Antagonists
- Aromatase Inhibitors
- Steroid Synthesis Inhibitors
- Estrogen Antagonists
- Letrozole
Other Study ID Numbers
- D20148
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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