Phase II Study of Alpelisib Combined with iNOS Inhibitor and Nab-paclitaxel for HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer

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.

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