Estradiol in Treating Patients With ER Beta Positive, Triple Negative Locally Advanced or Metastatic Breast Cancer

Anatomic Stage III Breast Cancer AJCC v8 Clinical Trial

Official title: Therapeutic Targeting of ER Beta in Triple Negative Breast Cancer

Status Enrolling by invitation

Clinical Trial Summary

This phase II trial studies how well estradiol works in treating patients with estrogen receptor beta (ER beta) positive, triple negative breast cancer that has spread to nearby tissue or lymph nodes (locally advanced) or other places in the body (metastatic). Hormone receptors like ER beta allow the body to respond appropriately to hormones. Triple negative means that the breast cancer does not express other hormone receptors called ER alpha, progesterone, and HER2. In some people with triple negative breast cancer, ER beta is overexpressed. Tumor cells that overexpress ER beta grow slower in the laboratory and this growth is slowed in the presence of estrogen. Estradiol is a form of estrogen. This study may help doctors determine whether tumor cells that overexpress ER beta shrink in the presence of estradiol.

Clinical Trial Description

PRIMARY OBJECTIVE:

I. To assess the anti-tumor activity of estradiol in patients with locally advanced or metastatic triple negative breast cancer (TNBC) that expresses ERbeta (> 25% moderate or strong nuclear staining).

SECONDARY OBJECTIVES:

I. To examine the safety profile of estradiol when administered at a dose of 2 mg three times daily (TID) to women with locally advanced or metastatic TNBC that expresses ERbeta.

II. To examine the changes in phosphorylated (phospho)-ERbeta, cystatins 1, 2, 4 and 5, phospho-Smad2/3 and Ki-67 in tumor biopsies taken before and after the first cycle of treatment.

EXPLORATORY OBJECTIVES:

I. To examine changes in plasma estradiol, serum cytokine and cystatin levels before/after 1 cycle of estradiol.

II. Analyze the global gene expression profiles of paired biopsies prior to and following 1 cycle of therapy.

III. To develop patient derived xenografts (PDX) that are ERalpha negative, HER2 negative and ERbeta positive (Mayo only).

IV. To examine changes in the relative abundance of circulating immune cell populations after the first cycle of treatment and whether these changes differ with respect to whether the patient is still on treatment after 6 cycles of treatment or not.

OUTLINE:

Patients receive estradiol orally (PO) TID for days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo a tissue biopsy at the end of cycle 1, collection of blood samples on day 1 of cycle 1 (C1D1), at the end of cycle 1, and at the end of treatment. In addition, patients undergo computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans at baseline, at the end of cycles 2, 4, and 6, and then every 8 weeks until disease progression.

After completion of study treatment, patients are followed up annually for 5 years from study registration. ;

Related Conditions & MeSH terms

• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Breast Neoplasms
• Carcinoma
• Metastatic Triple-Negative Breast Carcinoma
• Recurrent Breast Carcinoma

• NCT number: NCT03941730
• Study type: Interventional
• Source: Mayo Clinic
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: August 28, 2019
• Completion date: July 31, 2026