NCT03207529

Alpelisib and Enzalutamide in Treating Patients With Androgen Receptor and PTEN Positive Metastatic Breast Cancer

Phase Ib Study of BYL719 (Alpelisib) in Combination With Androgen Receptor Inhibitor (Enzalutamide) in Patients With Androgen Receptor (AR)-Positive and PTEN Positive Metastatic Breast Cancer

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (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 alpelisib when given together with enzalutamide in treating patients with androgen receptor and PTEN positive breast cancer that has spread to other places in the body. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Androgen receptor can cause the growth of breast cancer cells. Hormone therapy using enzalutamide may fight breast cancer by lowering the amount of androgen the body makes. Giving alpelisib and enzalutamide may work better in treating patients with breast cancer.

Detailed description

PRIMARY OBJECTIVE: I. To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of the combination of alpelisib (BYL719) and enzalutamide in patients with androgen receptor (AR)-positive and PTEN-positive metastatic breast cancer. SECONDARY OBJECTIVES: I. To determine the dose-limiting toxicity (DLT) of the combination of BYL179 and enzalutamide. II. To determine the safety profile of BYL179 and enzalutamide used in combination. III. Progression-free survival (PFS) and clinical benefit rate (CBR) (complete response or partial response + prolonged stable disease) after a 16-week treatment of BYL719 and enzalutamide per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. EXPLORATORY OBJECTIVES: I. To determine the association between aberrant circulating tumor cells (CTCs), circulating tumor deoxyribonucleic acid (ctDNA), and CBR at 16 weeks. II. To determine the association between PIK3CA and PTEN mutations and treatment response to the combination of BYL179 and enzalutamide. III. To determine the association between PIK3CA mutation status change in ctDNA and treatment response. IV. To determine the molecular (CTC, ctDNA) profile of tumors that become resistant to treatment in comparison with those prior to treatment. V. To determine the association between the AR expression level measured by immunohistochemistry (IHC) staining of tumor and CBR at 16 weeks. OUTLINE: This is a dose-escalation study of alpelisib. Patients receive alpelisib orally (PO) and enzalutamide PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.

Conditions

• Advanced Breast Carcinoma
• Anatomic Stage III Breast Cancer AJCC v8
• Anatomic Stage IIIA Breast Cancer AJCC v8
• Anatomic Stage IIIB Breast Cancer AJCC v8
• Anatomic Stage IIIC Breast Cancer AJCC v8
• Anatomic Stage IV Breast Cancer AJCC v8
• Androgen Receptor Positive
• HER2/Neu Negative
• Metastatic Breast Carcinoma
• Prognostic Stage III Breast Cancer AJCC v8
• Prognostic Stage IIIA Breast Cancer AJCC v8
• Prognostic Stage IIIB Breast Cancer AJCC v8
• Prognostic Stage IIIC Breast Cancer AJCC v8
• Prognostic Stage IV Breast Cancer AJCC v8
• PTEN Positive
• Recurrent Breast Carcinoma
• Refractory Breast Carcinoma
• Triple-Negative Breast Carcinoma

Interventions

Type	Name	Description
DRUG	Alpelisib	Given PO
DRUG	Enzalutamide	Given PO

Timeline

• Start date: 2019-06-07
• Primary completion: 2023-12-31
• Completion: 2023-12-31
• First posted: 2017-07-02
• Last updated: 2024-10-10

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study