Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03207529
Recruitment Status : Recruiting
First Posted : July 2, 2017
Last Update Posted : August 26, 2019
Sponsor:
Collaborators:
National Cancer Institute (NCI)
Novartis
Astellas Pharma Global Development, Inc.
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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.

Condition or disease Intervention/treatment Phase
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 Estrogen Receptor Negative Estrogen Receptor Positive HER2/Neu Negative Metastatic Breast Carcinoma Progesterone Receptor Negative Progesterone Receptor Positive 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 Drug: Alpelisib Drug: Enzalutamide Phase 1

Detailed Description:

PRIMARY OBJECTIVES:

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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : June 7, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Treatment (alpelisib, enzalutamide)
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
Given PO
Other Names:
  • BYL719
  • Phosphoinositide 3-kinase Inhibitor BYL719

Drug: Enzalutamide
Given PO
Other Names:
  • ASP9785
  • MDV3100
  • Xtandi




Primary Outcome Measures :
  1. Maximum tolerated dose (MTD) of alpelisib in combination with enzalutamide [ Time Frame: Up to 28 days ]

Secondary Outcome Measures :
  1. Incidence of adverse events [ Time Frame: Up to 16 weeks ]
    Standard descriptive analysis will be used to summarize the data.

  2. Profession-free survival (PFS) [ Time Frame: up to 16 weeks ]
    Will be estimated using Kaplan-Meier survival curves.

  3. Clinical benefit rate (CBR) (complete response or partial response + prolonged stable disease) [ Time Frame: Up to 16 weeks ]
    Will be evaluated according to RECIST version 1.1. Standard descriptive analysis will be used to summarize the data.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient has signed the informed consent form prior to the performance of any screening procedures and is able to comply with protocol requirements.
  • Patient has advanced or metastatic breast cancer that is refractory to at least one standard therapy or that has relapsed after standard therapy or that has no standard systemic therapy that increases survival by at least 3 months.
  • 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
  • Fasting plasma glucose (FPG) =< 140 mg/dL or =< 7.8 mmol/L
  • Patient is able to swallow and retain oral medication and does not have any clinically significant gastrointestinal abnormalities that may alter drug absorption, such as malabsorption syndrome or major resection of the stomach or bowels.
  • For dose-escalation cohort, patient has at least 1 measurable disease as defined by RECIST criteria (Version 1.1). For dose-expansion cohort, patient has at least 1 measurable disease as defined by RECIST criteria (version 1.1) with a lesion larger than 1.5 cm that can be biopsied by core needle biopsy.
  • For dose-escalation portion of study, patients must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition.
  • Patient has a life expectancy of at least 3 months in the opinion of the investigator.

Exclusion Criteria:

  • 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).
  • Patient is currently receiving medication with a known risk of prolonging the QT interval or inducing torsades de pointes (TdP) and whose treatment cannot be either discontinued or switched to a different medication prior to starting treatment with the study drug.
  • Patient has any prior use of PI3K inhibitors.
  • Patient has any prior use of anti-androgen therapies.
  • Patient is currently receiving warfarin or other Coumarin-derived anticoagulant for treatment, prophylaxis, or other reasons. Therapy with heparin, low molecular weight heparin, or fondaparinux is allowed.
  • Patient is currently receiving treatment with drugs known to be strong inhibitors or inducers of isoenzymes CYP3A or CYP2C8. The patient must have discontinued strong inducers for at least 1 week and must have discontinued strong inhibitors before the start of the study treatment. Switching to a different medication prior to initiation of the trial treatment is allowed.
  • Patient has impaired gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral BYL719 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  • Patient has known positive serology for human immunodeficiency virus (HIV).
  • Patient has any other condition that would, in the investigators' judgment, preclude the patient's participation in the clinical study due to concerns about safety or compliance with clinical study procedures; e.g., infection/inflammation, intestinal obstruction, inability to swallow oral medication, social/psychological complications.
  • Patient has a history of noncompliance to medical regimens or is unable to grant consent.
  • Female patients of childbearing potential have positive urine or serum pregnancy test no more than 7 days prior to starting study drug.
  • Female patients of childbearing potential are not willing to use highly effective contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study. Highly effective contraception is defined as:

    • Surgical birth control/sterilization (such as male vasectomy or female sterilization).
    • Birth control pills, injections, implants, or patches.
    • Intrauterine devices (IUDs).
    • Two barrier methods (male condom and female diaphragm, cervical cap, or sponge) in combination with a spermicide.
    • Highly effective contraception must be used by both sexes during the study and must be continued for 6 months after the last dose of study treatment. (Women of not childbearing potential: post-menopausal [age > 55 years with cessation of menses > 12 months or < 55 years but not spontaneous menses for at least 2 years or < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), and with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved] or who have had a hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
  • Female patients who are breast-feeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03207529


Contacts
Layout table for location contacts
Contact: Meghan S. Karuturi, MD 713-792-2817 mskaruturi@mdanderson.org

Locations
Layout table for location information
United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Meghan Karuturi    713-792-2817      
Principal Investigator: Meghan Karuturi         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Novartis
Astellas Pharma Global Development, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Meghan Karuturi M.D. Anderson Cancer Center

Additional Information:
Layout table for additonal information
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03207529     History of Changes
Other Study ID Numbers: 2016-0538
NCI-2018-01127 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2016-0538 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: August 26, 2019
Last Verified: August 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma
Breast Neoplasms
Triple Negative Breast Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Androgens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs