Actively Recruiting

Phase 2
Age: 18Years +
All Genders
ID05660083

Phase II Trial of Alpelisib With iNOS Inhibitor and Nab-paclitaxel in Patients With HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer (MpBC)

Led by The Methodist Hospital Research Institute · Updated on 2026-06-04

36

Participants Needed

3

Research Sites

104 weeks

Total Duration

On this page

Sponsors

T

The Methodist Hospital Research Institute

Lead Sponsor

N

Novartis Pharmaceuticals

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are evaluating the safety and effectiveness of combining the drug alpelisib with chemotherapy (nab-paclitaxel) and an iNOS inhibitor called L-NMMA in patients with HER2 negative metastatic or locally advanced metaplastic breast cancer (MpBC) who have not responded to previous treatments. MpBC is a rare and aggressive subtype of triple-negative breast cancer (TNBC) that is resistant to chemotherapy and has a poor prognosis. This Phase II trial aims to improve treatment response by targeting pathways linked to chemotherapy resistance using this combination approach. Participants will receive standard chemotherapy with nab-paclitaxel intravenously on Day 1 every 3 weeks (one cycle). Alongside this, they will take alpelisib by mouth daily at a dose determined by earlier safety studies. The iNOS inhibitor L-NMMA will be given intravenously on Days 1 through 5 of each 3-week cycle. Treatment continues until disease progression, unacceptable side effects, or withdrawal. Additional medications such as aspirin and amlodipine are used to prevent side effects, and metformin is given to manage blood sugar levels during the study. During the study, participants will be closely monitored with regular assessments including biopsies at baseline and after the second treatment cycle to analyze response and mutation status. Researchers will measure the recommended dose, objective response rate, progression-free survival, overall survival, and safety throughout an average of six cycles. Participants must comply with scheduled visits, take study medications, and report any side effects or changes in health during the study period.

CONDITIONS

Brief Title

Alpelisib/iNOS Inhibitor/Nab-paclitaxel in Patients With HER2 Negative Metaplastic Breast Cancer (MpBC)

Who Can Participate

Age: 18Years +
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Provide written informed consent for the study.
  • Be at least 18 years old at the time of consent.
  • Have histologically confirmed HER2 negative metaplastic breast cancer or triple negative breast cancer with specific tumor features.
  • HER2 negative status confirmed by current guidelines.
  • Have locally advanced inoperable or metastatic disease measurable by RECIST 1.1.
  • Eastern Cooperative Oncology Group performance status of 0 or 1.
  • Adequate organ and marrow function including specified blood counts and liver and kidney tests.
  • Fasting blood glucose ≤140 mg/dl and hemoglobin A1c ≤7.0.
  • Ability to swallow oral medication.
  • Ability to take aspirin.
  • Women of childbearing potential must agree to use contraception during the study and 90 days after.
  • Male participants must use condoms during the study and avoid sperm donation.
  • Recovered adequately from any major surgery before starting treatment.
  • Willing and able to comply with study protocol and visits.
Not Eligible

You will not qualify if you...

  • Use of strong CYP3A4 inhibitors or inducers within 1 week prior to treatment.
  • Current use of warfarin or coumarin-derived anticoagulants.
  • Use of medications interacting with nitrate/nitrite levels.
  • Previous treatment with nab-paclitaxel, PI3K inhibitor, AKT inhibitor, or mTOR inhibitor.
  • History of Steven Johnson's syndrome or toxic epidermal necrolysis.
  • HIV positive patients due to drug metabolism concerns.
  • Poorly controlled hypertension above 150 mm Hg systolic.
  • Certain cardiac conditions including congestive heart failure, cardiomyopathy, recent heart attack, unstable angina, arrhythmias, pericarditis, prolonged QT interval.
  • Participation in another investigational study within 3 weeks before treatment.
  • Known allergy to study drugs or components.
  • Additional malignancy requiring active treatment.
  • Pneumonitis or moderate to severe chronic lung disease.
  • Psychiatric or substance abuse disorders interfering with study compliance.
  • Malabsorption due to gastrointestinal conditions.
  • Untreated or symptomatic brain metastases.
  • Type I diabetes or uncontrolled type II diabetes.
  • Uncontrolled gastric ulcer.
  • Grade 2 or higher sensory neuropathy.
  • Osteonecrosis of the jaw.
  • Pancreatitis.
  • Pregnant, breastfeeding, or planning pregnancy during study and 30 days after last dose.

AI-Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - Approximately 18 weeks (an average of 6 cycles of 3 weeks each), continuing until disease progression, unacceptable toxicity, or withdrawal

Participants receive a combination of an iNOS inhibitor, nab-paclitaxel, and alpelisib to treat HER2 negative metastatic or locally advanced MpBC. Additional medications such as aspirin, amlodipine, metformin, and anti-histamines are given to manage side effects and prevent complications.

Visits every 3 weeks for treatment cycles

Trial Site Locations

Total: 3 locations

1

National Institute of Health Clinical Center

Bethesda, Maryland, United States, 20892

Actively Recruiting

2

Houston Methodist Neal Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

3

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States, 77030

Actively Recruiting

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Research Team

A

Alexys Brock

T

Titilayo Olubajo

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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Published Research Related To This Trial

Pharmacological Inhibition of NOS Activates ASK1/JNK Pathway Augmenting Docetaxel-Mediated Apoptosis in Triple-Negative Breast Cancer.

Daniel Dávila-González, Dong Soon Choi, Roberto R Rosato...

https://pubmed.ncbi.nlm.nih.gov/29301832

Impact of inducible nitric oxide synthase (iNOS) expression on triple negative breast cancer outcome and activation of EGFR and ERK signaling pathways.

Pablo Garrido, Aliaa Shalaby, Elaine M Walsh...

https://pubmed.ncbi.nlm.nih.gov/29113326

S-nitrosylation of EGFR and Src activates an oncogenic signaling network in human basal-like breast cancer.

Christopher H Switzer, Sharon A Glynn, Robert Y-S Cheng...

https://pubmed.ncbi.nlm.nih.gov/22878588

Phosphoinositide 3-kinase/Akt pathway plays an important role in chemoresistance of gastric cancer cells against etoposide and doxorubicin induced cell death.

Hong-Gang Yu, Yao-Wei Ai, Liang-Liang Yu...

https://pubmed.ncbi.nlm.nih.gov/17935137