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Advanced Breast CarcinomaPhase 1NCT03207529

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

A Phase 1 study testing Alpelisib and Enzalutamide in people with Advanced Breast Carcinoma and Anatomic Stage III Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alpelisib and Enzalutamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
18 participants
Where
1 siteUnited States
Study dates
7 Jun 2019to 31 Dec 2023
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Alpelisib, Enzalutamide
Medical subject headings
Breast Neoplasms, Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AlpelisibDrug

    Also called BYL719, Phosphoinositide 3-kinase Inhibitor BYL719, Piqray

    Given PO

  • EnzalutamideDrug

    Also called ASP9785, MDV3100, Xtandi

    Given PO

Study groups in NCT03207529
Study groupRoleWhat they receive
Treatment (alpelisib, enzalutamide)ExperimentalPatients receive alpelisib PO and enzalutamide PO on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: Alpelisib; Drug: Enzalutamide

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: Up to 28 days

Secondary outcomes (3)

  1. Incidence of adverse events

    Standard descriptive analysis will be used to summarize the data.

    Measured: Up to 16 weeks

  2. Profession-free survival (PFS)

    Will be estimated using Kaplan-Meier survival curves. From cycle 1 day 1 (cycle 1 is 28 days) to that of disease progression per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or death, whichever comes earlier, assessed up to 16 weeks]

    Measured: Up to 16 weeks

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

    Will be evaluated according to RECIST version 1.1. Standard descriptive analysis will be used to summarize the data.

    Measured: Up to 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2017
  2. Study start7 Jun 2019
  3. Primary completion31 Dec 2023
  4. Study completion31 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
18 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03207529
Sponsor's protocol ID
2016-0538
Other IDs
NCI-2018-01127, 2016-0538
Status last verified
Oct 2024
First submitted
30 Jun 2017
Last updated
10 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Alpelisib and Enzalutamide in people with Advanced Breast Carcinoma and Anatomic Stage III Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 20 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum tolerated dose (MTD) of alpelisib in combination with enzalutamide (time frame: Up to 28 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03207529.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2024.

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