Effect of HSD3B1 (1245C) Gene Mutation on Treatment of Stage I-III Breast Cancer

NCT05183828 | Recruiting Phase 4 DMC FDA Drug

• 4 other identifiers: RG1121659NCI-2021-12428IR10794P30CA015704
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

This stage IV trial examines how a mutation in HSD3B1 (1245C) gene affects treatment of stage I-III breast cancer. This trial may help researchers determine if mutations in HSD3B1 decreases the efficacy of aromatase inhibitor therapy such as letrozole. Letrozole may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Breast Adenocarcinoma; Invasive Breast Carcinoma of No Special Type

Outcome Measures

Primary Outcomes (10)

• Changes in Ki67

  Will be assessed according to germline status.

  Before (baseline) and up to 9 months after surgery

• Changes in Ki67

  Will be assessed according to somatic HSD3B1 (1245C) variant status.

  Before (baseline) and up to 9 months after surgery

• Changes in estrogen receptor (ER)alpha

  Will be assessed according to germline status.

  Before (baseline) and up to 9 months after surgery

• Changes in estrogen receptor (ER)alpha

  Will be assessed according to somatic HSD3B1 (1245C) variant status.

  Before (baseline) and up to 9 months after surgery

• Changes in ER beta

  Will be assessed according to germline status.

  Before (baseline) and up to 9 months after surgery

• Changes in ER beta

  Will be assessed according to somatic HSD3B1 (1245C) variant status.

  Before (baseline) and up to 9 months after surgery

• Effect of HSD3B1 (1245C) variant on changes in Ki67

  Will evaluate whether androgen receptor (AR)+ modifies the effect of HSD3B1 (1245C) variant on changes in Ki67 before and after preoperative letrozole treatment, and whether this effects ER- and AR- gene expression signatures.

  Before (baseline) and up to 9 months after surgery

• Expression of 3betaHSD1

  Will compare expression of 3betaHSD1 according to HSD3B1 allele status.

  Up to 9 months after surgery

• Expression of intracellular androgen

  Will compare expression of intracellular androgen according to HSD3B1 allele status.

  Up to 9 months after surgery

• Expression of estrogen levels

  Will compare expression of estrogen levels according to HSD3B1 allele status.

  Up to 9 months after surgery

Study Arms (1)

Treatment (letrozole)

EXPERIMENTAL

Patients receive letrozole PO QD for 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of saliva samples. If tumor resection occurs before or after day 22, letrozole administration must occur for a minimum of 14 days and a maximum of 70 days of total treatment.

Procedure: Biospecimen Collection; Drug: Letrozole; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of saliva samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (letrozole)

Letrozole DRUG

Given PO

Also known as: CGS 20267, Femara

Treatment (letrozole)

Questionnaire Administration OTHER

Ancillary studies

Treatment (letrozole)

Eligibility Criteria

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

You may qualify if:

• Subject must be female age \>= 18 years.
• Postmenopausal as defined by at least one of the following:
• Age \>= 60 years;
• Age \< 60 years and cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; or serum estradiol and follicle stimulating hormone levels within the local laboratory's normal reference range for postmenopausal females;
• Documented bilateral oophorectomy.
• Histologically confirmed diagnosis of carcinoma of the breast, clinical stage I-III.
• Minimum tumor diameter of 1.0 cm as assessed by palpation or imaging (e.g., ultrasound) and with enough tumor left after the initial diagnostic biopsy to provide tumor tissue during the planned tumor resection.
• Candidate for surgical resection.
• ER+ breast cancer (\> 1% positive stained cells) based on the most recent tumor biopsy documented by a local laboratory or medical record.
• Ki67 \>= 10%.
• HER2-negative breast cancer based on the most recent tumor biopsy and documented by a local laboratory or medical record. HER2-negative tumor is defined per American Society of Clinical Oncology and the College of American Pathologists guidelines, 2018.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Prior use of hormone contraceptives and replacement therapy is allowed (e.g., estrogen and/or progestin) if discontinued \> 6 months prior to diagnosis. Vaginal preparations are allowed.
• Ability to take oral medication and be willing to adhere to the study intervention.

You may not qualify if:

• Pre-treatment tumor biopsy sample not likely to provide adequate tissue sections for biomarker assays.
• Inoperable or metastatic disease.
• Subjects who have received any prior therapy for breast cancer, including radiotherapy, surgery, and cytotoxic and endocrine treatments.
• The subject must not have had hormonal therapy for breast cancer treatment or for breast cancer prevention within 1 year prior to study enrollment. (Note: Synchronous breast, cancer (including bilateral breast cancer) at separate sites is permissible, provided the patient does not receive medical treatments for breast cancer or radiation therapy to the ipsilateral breast during the study intervention period.
• Subjects with plans to undergo neoadjuvant chemotherapy.
• Use of hormonal contraceptives within 6 months of diagnosis.
• Treatment with another investigational drug or other intervention within 28 days before the first administration of letrozole.
• History of allergic reactions/hypersensitivity attributed to compounds of similar chemical or biologic composition to letrozole or any ingredients.
• Uncontrolled current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Ductal

Interventions

Specimen Handling; Letrozole

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Meghan R. Flanagan

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meghan R. Flanagan

CONTACT

206-667-6736; mrf22@uw.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2021
• First Posted: January 11, 2022
• Study Start: January 23, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)