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Anatomic Stage I Breast Cancer AJCC v8Phase 2NCT04216472

Nab-paclitaxel and Alpelisib for the Treatment of Anthracycline Refractory Triple Negative Breast Cancer With PIK3CA or PTEN Alterations

A Phase 2 study testing Alpelisib and Nab-paclitaxel in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage IA Breast Cancer AJCC v8, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well nab-paclitaxel and alpelisib works in treating patients with triple negative breast cancer with PIK3CA or PTEN alterations that does not respond to anthracycline chemotherapy (anthrocycline refractory). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Alpelisib and Nab-paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
10 Jul 2020to 22 Sep 2025
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
  • Stage I-III breast cancer
  • Confirmed invasive triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and HER2 negative by American Society of Clinical Oncology (ASCO)/(College of American Pathologists) CAP guidelines
  • Activating mutations in PIK3CA (cohort-1), or loss of function alterations in PTEN by next generation sequencing (NGS) or IHC (cohort-2) (based on MD Anderson Cancer Center [MDACC] Dako 6H2.1 assay)
  • Fasting plasma glucose (FPG) =< 140 mg/dL (7.7 mmol/L) and glycosylated hemoglobin (HbA1c) < 6.4 %
  • For patients with pre-diabetes (FPG >= 100 mg/dL and/or HbA1c >= 5.7%) at screening, recommend lifestyle changes according to American Diabetes Association (ADA) guidelines. A consultation with a diabetologist is highly recommended
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  • Chemotherapy insensitive disease as defined by ARTEMIS parameters (=< 70 % volumetric response after four cycles of anthracycline-based therapy)
  • Residual primary tumor size of at least 1.0 cm by imaging (ultrasound or MRI) or evidence of lymph node involvement by imaging (ultrasound or MRI) after anthracycline-based neoadjuvant chemotherapy (NACT)
  • Received at least one dose of an anthracycline-based NACT. Patients are eligible if therapy was discontinued due to disease progression or therapy intolerance
  • Prior to participation on ARTEMIS trial (2014-0185) multigated acquisition scan (MUGA) or echocardiogram showing left ventricular ejection fraction (LVEF) >= 50%
  • Absolute neutrophil count (ANC) >= 1.5 x 10^9 /L
  • Platelets >= 100 x 10^9 /L
  • Hemoglobin (Hb) > 9 g/dL
  • Fasting serum amylase =< 2 x upper limit of normal (ULN)
  • Fasting serum lipase =< ULN
  • Total serum bilirubin =< 1.5 mg/dL
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert's syndrome
  • Serum creatinine =< 1.5 x ULN or and/or creatinine clearance > 50% lower limit of normal (LLN)
  • Signed informed consent obtained prior to any screening procedures
  • Patients must have at least 2 and no more than 5 weeks between anthracycline-based therapy and start of treatment with alpelisib and nab-paclitaxel
  • Patients must have resolution of toxic effect(s) of the most recent prior chemotherapy to grade 1 or less (except alopecia)
  • Women of childbearing potential (WCBP) must have a negative pregnancy test within 3 days prior to the first dose of study treatment. WCBP (defined as all women physiologically capable of becoming pregnant) must use highly effective methods of contraception during the study and 12 weeks after. Highly effective contraception methods include a combination of any two of the following:
  • Placement of an intrauterine device (IUD) or intrauterine system (IUS)
  • Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
  • Total abstinence
  • Male/ female sterilization

Who cannot join

  • Pregnant or lactating women
  • Patient has a known hypersensitivity to alpelisib or any of its excipients
  • Patients with clinically manifest diabetes mellitus (DM) or documented steroid induced DM
  • Presence of distant metastatic disease (loco-regional nodal involvement of the ipsilateral axillary, internal mammary and/or supraclavicular nodes is not considered distant metastatic disease
  • Prior radiation therapy of the primary breast carcinoma or axillary lymph nodes
  • Patient is concurrently using other anti-cancer therapy
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  • Patients with an established diagnosis of diabetes mellitus type II or uncontrolled type II based on fasting plasma glucose or HbA1c
  • Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study
  • Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of alpelisib
  • Male patients whose sexual partner(s) are WCBP who are not willing to use adequate contraception, during the study and for 4 weeks after the end of treatment
  • Patients with > grade 1 peripheral neuropathy
  • Patients being treated with drugs recognized as being strong inhibitors or inducers of the isoenzyme CYP3A within the last 5 days prior to study entry
  • Serious concurrent illness or clinically-relevant active infection, including, but not limited to the following:
  • Known active hepatitis B or C
  • Known human immunodeficiency virus (HIV) infection
  • Varicella-zoster virus (shingles)
  • Cytomegalovirus infection
  • Any other known concurrent infectious disease, requiring IV antibiotics within 2 weeks of study enrollment
  • Clinically- significant cardiac disease:
  • Recent myocardial infarction (< 6 months prior to day 1)
  • Unstable angina pectoris
  • Uncontrolled congestive heart failure (New York Heart Association > class II)
  • Uncontrolled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Uncontrolled cardiac arrhythmias
  • Clinically-significant vascular disease (e.g. aortic aneurysm dissecting aneurysm)
  • Severe aortic stenosis
  • Clinically significant peripheral vascular disease
  • Friderica's Corrected QT interval (QTcF) > 470 for females and > 450 for males
  • History of neurological conditions that would confound assessment of treatment-emergent neuropathy
  • History of hemorrhagic or ischemic stroke within the last 6 months
  • Patient with severe liver impairment (Child Pugh score B/C) or cirrhotic liver disease
  • Patient has documented history of pneumonitis/interstitial lung disease
  • History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
  • Patients who have a history of another primary malignancy, with the exceptions of: non-melanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for 3 years
  • History or evidence of thrombotic or hemorrhagic disorders within 6 months before first study treatment

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: A Phase-2, Two-Cohort Trial of Neoadjuvant Nab-Paclitaxel and Alpelisib in Anthracycline Refractory Triple Negative Breast Cancer With PIK3CA or PTEN Alterations

This phase II trial studies how well nab-paclitaxel and alpelisib works in treating patients with triple negative breast cancer with PIK3CA or PTEN alterations that does not respond to anthracycline chemotherapy (anthrocycline refractory). Drugs used in chemotherapy, such as nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving nab-paclitaxel and alpelisib before surgery may help shrink the tumor before surgery.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine if alpelisib in combination with nab-paclitaxel in the neoadjuvant setting will improve rates of pathologic response (pathological complete response [pCR/RCB-0] or minimal residual disease [RCB-I]) from 5% to 20% in patients with chemotherapy insensitive triple negative breast cancer (TNBC) with PIK3CA alterations (including PTEN loss). (Cohort 1) II. To determine if alpelisib in combination with nab-paclitaxel in the neoadjuvant setting will improve rates of pathologic response (pCR/RCB-0 or RCB-I) from 5% to 20% in patients with chemotherapy insensitive TNBC with PTEN alterations. (Cohort 2)

SECONDARY OBJECTIVES:

  1. Determine the radiographic response rate for alpelisib in combination with nab-paclitaxel as measured by ultrasound and/or magnetic resonance imaging (MRI) (partial response + complete clinical response) in chemotherapy insensitive TNBC with PIK3CA (Cohort-1) or PTEN (Cohort-2) alterations.

II. Determine toxicity of alpelisib in combination with nab-paclitaxel given in the neoadjuvant setting following anthracycline based therapy.

III. Determine progression free survival (PFS) at 3 years for patients treated with alpelisib in combination with nab-paclitaxel given in the neoadjuvant setting in chemotherapy insensitive TNBC with PIK3CA (Cohort-1) or PTEN (Cohort-2) alterations.

EXPLORATORY OBJECTIVES:

  1. To assess biomarkers of response and resistance to alpelisib and nab-paclitaxel combination.

II. To assess the role of circulating tumor deoxyribonucleic acid (ctDNA) allele fraction in predicting response to alpelisib and nab-paclitaxel in early stage TNBC.

OUTLINE:

Patients receive alpelisib orally (PO) once daily (QD) on days 1-21, and nab-paclitaxel intravenously (IV) over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may then undergo surgery to remove the tumor.

After completion of study treatment, patients are followed up at 30 days, and then periodically until up to 3 years after surgery.

Being tested
Alpelisib, Nab-paclitaxel
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

  • Nab-paclitaxelDrug

    Also called ABI 007, ABI-007, Abraxane, Albumin-bound Paclitaxel

    Given IV

Study groups in NCT04216472
Study groupRoleWhat they receive
Treatment (alpelisib, nab-paclitaxel)ExperimentalPatients receive alpelisib PO QD on days 1-21, and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 21 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients may then undergo surgery to remove the tumor.
Receives: Drug: Alpelisib; Drug: Nab-paclitaxel

What is being measured

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

  1. Rate of Pathological Complete Response (pCR/RCB-0)

    Will be assessed by the alpelisib in combination with nab-paclitaxel in the neoadjuvant setting will improve rates.

    Measured: Up to 30 days

Timeline

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

  1. First posted2 Jan 2020
  2. Study start10 Jul 2020
  3. Primary completion22 Sep 2025
  4. Study completion22 Sep 2025

Why it stopped: \<75% participation

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04216472
Sponsor's protocol ID
2019-0752
Other IDs
NCI-2019-08495, 2019-0752
Status last verified
Jun 2026
First submitted
31 Dec 2019
Last updated
7 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Alpelisib and Nab-paclitaxel in people with Anatomic Stage I Breast Cancer AJCC v8 and Anatomic Stage IA 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 26 inclusion and 36 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: stopped early, as of the sponsor's last update on 7 Jul 2026. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jul 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Rate of Pathological Complete Response (pCR/RCB-0) (time frame: Up to 30 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 NCT04216472.

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 7 Jul 2026.

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