NCT02152943

Everolimus, Letrozole and Trastuzumab in HR- and HER2/Neu-positive Patients

Combination Treatment With Everolimus, Letrozole and Trastuzumab in Hormone Receptor and HER2/Neu-Positive Patients With Advanced Metastatic Breast Cancer and Other Solid Tumors: Evaluating Synergy and Overcoming Resistance

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 37 (actual)
• Sponsor: M.D. Anderson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of everolimus and trastuzumab when given together with letrozole in treating patients with hormone receptor-positive and human epidermal growth factor (EGF) receptor 2 (HER2)-positive breast cancer or other solid tumors that have spread to other places in the body. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by tumor cells. Immunotherapy with monoclonal antibodies, such as trastuzumab, may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving everolimus, letrozole, and trastuzumab together may be a better treatment for breast cancer and other solid tumors than everolimus alone.

Detailed description

PRIMARY OBJECTIVES: I. Determine reasonable dose of drugs in treatment combination, including maximum tolerated dose (MTD) and toxicity profiles, via a brief initial "run-in"/dose escalation. II. Evaluate response, in patients with tumors that demonstrate hormone receptor (HR)-positivity (\> 1% on immunohistochemistry \[IHC\]) and human EGF receptor 2 (HER)-positivity (IHC 3 and/or IHC 2/3 and fluorescence in situ hybridization \[FISH\] amplification). SECONDARY OBJECTIVES: I. Correlate activity of combination with genomic and proteomic signatures. II. Evaluate 2 expanded cohorts of patients to include: 1) HR- and HER2-positive breast cancer (n=12) and 2) other HR- and HER2-positive tumors that have demonstrated activity in the dose escalation portion of the study (n=12). OUTLINE: This is a dose-escalation study of everolimus and trastuzumab. Patients receive everolimus orally (PO) once daily (QD) and letrozole PO QD. Patients also receive trastuzumab intravenously (IV) over 30-90 minutes once every 3 weeks. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 30 days.

Conditions

• Advanced Malignant Solid Neoplasm
• Estrogen Receptor Positive
• HER2/Neu Positive
• Postmenopausal
• Premenopausal
• Progesterone Receptor Positive
• Recurrent Breast Carcinoma
• Refractory Breast Carcinoma
• Refractory Hormone Receptor Positive Breast Carcinoma
• Stage IIIA Breast Cancer AJCC v7
• Stage IIIB Breast Cancer AJCC v7
• Stage IIIC Breast Cancer AJCC v7
• Stage IV Breast Cancer AJCC v6 and v7

Interventions

Type	Name	Description
DRUG	Everolimus	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Letrozole	Given PO
BIOLOGICAL	Trastuzumab	Given IV

Timeline

• Start date: 2014-07-17
• Primary completion: 2020-12-14
• Completion: 2020-12-14
• First posted: 2014-06-02
• Last updated: 2020-12-19

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study