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

NCT03207529 | Completed Phase 1 FDA Drug

• 2 other identifiers: 2016-0538NCI-2018-01127
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD) of alpelisib in combination with enzalutamide

  Up to 28 days

Secondary Outcomes (3)

• Incidence of adverse events

  Up to 16 weeks

• Profession-free survival (PFS)

  Up to 16 weeks

• Clinical benefit rate (CBR) (complete response or partial response + prolonged stable disease)

  Up to 16 weeks

Study Arms (1)

Treatment (alpelisib, enzalutamide)

EXPERIMENTAL

Patients receive alpelisib PO and enzalutamide PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Alpelisib; Drug: Enzalutamide

Interventions

Alpelisib DRUG

Given PO

Also known as: BYL719, Phosphoinositide 3-kinase Inhibitor BYL719, Piqray

Treatment (alpelisib, enzalutamide)

Enzalutamide DRUG

Given PO

Also known as: ASP9785, MDV3100, Xtandi

Treatment (alpelisib, enzalutamide)

Eligibility Criteria

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

You may qualify if:

• Patient is \>/= 18 years old.
• Patient has signed the informed consent form prior to the performance of any screening procedures and is able to comply with protocol requirements.
• Patients with central nervous system (CNS) involvement unless they meet ALL of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery to starting the study treatment) \* Clinically and radiographically stable CNS tumor at the time of screening and not receive steroids and/or an enzyme inducing anti-epileptic mediations for brain metastasis
• Absence of leptomeningeal disease
• Patient has metastatic breast cancer that is not suitable for surgery or radiation therapy for local disease control at the time of screening.
• Patient has disease that is hormone-receptor positive (estrogen receptor \[ER\] and/or progesterone receptor \[PR\] positive \[+\], HER-2/neu negative \[-\]) or triple-negative (ER/PR/HER-2/neu -).
• Patient has an AR-positive and PTEN-positive tumor as determined by using Clinical Laboratory Improvement Amendments (CLIA) compliant assays to identify AR-positive and PTEN-positive disease (AR positivity is defined as \>= 1% of nuclear staining, PTEN positivity is defined as \> 0% of nuclear staining).
• Patient has an Eastern Cooperative Oncology Group performance status (ECOG PS) =\< 1 that the investigator believes is stable at the time of screening.
• Absolute neutrophil count (ANC) \>= 1.0 x 10\^9/L
• Platelets \>= 100 x 10\^9/L
• Hemoglobin \>= 9.0 g/dL
• Serum creatinine =\< 1.5 x upper limit of normal (ULN)
• Total serum bilirubin =\< 1.5 x ULN
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN; in the event of liver metastasis, AST/ALT =\< 5 ULN

You may not qualify if:

• Patient has a known hypersensitivity to any of the excipients of BYL719 and/or enzalutamide.
• Patient has a known or suspected primary central nervous system (CNS) tumor or CNS tumor involvement or active leptomeningeal disease.
• Patient has a history of seizures or any condition that may predispose to seizures (e.g., prior cortical stroke, significant brain trauma) at any time in the past and/or a history of loss of consciousness or transient ischemic attack within 12 months of the cycle 1, day 1 visit.
• Patient has uncontrolled diabetes.
• Patient has a history of another malignancy within 2 years prior to starting study treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in situ of the cervix.
• Patient has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) (version 4.03) grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy.
• Patient has had any systemic therapy within 2 weeks prior to initiating study drug.
• Patient has participated in a prior investigational study within 3 weeks prior to initiating study drug.
• Patient has completed radiotherapy within 2 weeks prior to treatment initiation.
• Patient has any serious and/or unstable pre-existing medical disorder (aside from malignancy exception above), psychiatric disorder, or other conditions that could interfere with patient's safety, provision of informed consent, or compliance with the study procedures.
• Patient has known clinically significant cardiac disease or impaired cardiac function, such as:
• Congestive heart failure requiring treatment (New York Heart Association grade \>= 2), left ventricular ejection fraction (LVEF) \< 50% as determined by multigated acquisition (MUGA) scan or ECHO.
• History or current evidence of clinically significant cardiac arrhythmias, atrial fibrillation, and/or conduction abnormality, e.g., congenital long QT syndrome, high-grade/complete arteriovenous blockage.
• Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft, coronary angioplasty, or stenting) \< 3 months prior to screening.
• Patient has a QT interval adjusted by the Fridericia formula (QTcF) \> 480 msec on screening electrocardiogram (ECG).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

Alpelisib; enzalutamide

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Meghan Karuturi

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2017
• First Posted: July 2, 2017
• Study Start: June 7, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: October 10, 2024

Record last verified: 2024-10

Locations

US (1)