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

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title:

Association of HSD3B1 Genotype With Response to Preoperative Letrozole Therapy Among Postmenopausal Women With Estrogen-Receptor Positive (ER+) HER2/Neu-Negative (HER2-) Invasive Carcinomas of the Breast

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05183828
• Other study ID #: RG1121659
• Secondary ID: NCI-2021-12428ST
• Status: Recruiting
• Phase: Phase 4
• Start date: January 23, 2022
• Est. completion date: December 31, 2024

Study information

• Verified date: January 2024
• Source: University of Washington
• Contact: Meghan R. Flanagan
• Phone: 206-667-6736
• Email: mrf22[@]uw.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

OUTLINE:

Patients receive letrozole orally (PO) once daily (QD) for 21 days in the absence of disease progression or unacceptable toxicity. 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. Patients also undergo collection of saliva samples.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• 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). Vaginal preparations are allowed.

• Ability to take oral medication and be willing to adhere to the study intervention.

Exclusion Criteria:

• 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 for the current breast cancer, or received any therapy within the last 1 year for a prior primary breast cancer.

• 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.

• 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.

Related Conditions & MeSH terms

• Anatomic Stage I Breast Cancer AJCC v8
• Anatomic Stage II Breast Cancer AJCC v8
• Anatomic Stage III Breast Cancer AJCC v8
• Breast Adenocarcinoma
• Breast Neoplasms
• Carcinoma
• Carcinoma, Ductal, Breast

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of saliva samples

Drug:
• Letrozole
Given PO

Other:
• Questionnaire Administration
Ancillary studies

Locations

Country	Name	City	State
United States	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
University of Washington	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Ki67	Will be assessed according to germline status.	Before (baseline) and up to 9 months after surgery
Primary	Changes in Ki67	Will be assessed according to somatic HSD3B1 (1245C) variant status.	Before (baseline) and up to 9 months after surgery
Primary	Changes in estrogen receptor (ER)alpha	Will be assessed according to germline status.	Before (baseline) and up to 9 months after surgery
Primary	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
Primary	Changes in ER beta	Will be assessed according to germline status.	Before (baseline) and up to 9 months after surgery
Primary	Changes in ER beta	Will be assessed according to somatic HSD3B1 (1245C) variant status.	Before (baseline) and up to 9 months after surgery
Primary	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
Primary	Expression of 3betaHSD1	Will compare expression of 3betaHSD1 according to HSD3B1 allele status.	Up to 9 months after surgery
Primary	Expression of intracellular androgen	Will compare expression of intracellular androgen according to HSD3B1 allele status.	Up to 9 months after surgery
Primary	Expression of estrogen levels	Will compare expression of estrogen levels according to HSD3B1 allele status.	Up to 9 months after surgery