Phase II Trial of Alpelisib With iNOS Inhibitor and Nab-paclitaxel in Patients With HER2 Negative Metastatic or Locally Advanced Metaplastic Breast Cancer (MpBC)
This is a research study to test the safety and effectiveness of using the drug alpelisib together with chemotherapy (nab-paclitaxel) and a drug called L-NMMA in patients with HER2 negative metastatic or locally advanced metaplastic breast cancer, who have not responded to previous treatments. Participants in this study in addition to the standard care chemotherapy will also receive the drug alpelisib and L-NMMA. The therapies will be administered every 3 weeks (1 cycle) until disease progression, toxicity or until the participant withdraws from the study. The nab-paclitaxel chemotherapy will be administered intravenously on Day 1 of the 3 week cycles. Participants will take the drug alpelisib by mouth once daily at a dose determined by a safety study and the drug L-NMMA will be given intravenously on days 1 to 5 of the 3 week cycles.
• The patient (or legally acceptable representative if applicable) provides written informed consent for the study.
• At least 18 years of age on the day of informed consent signing.
• Histologically confirmed HER2 negative MpBC and/or Triple Negative Breast Cancer (TNBC) with squamous and/or sarcomatoid elements, including osseous, chondroid, and spindle morphology.
• HER2 negative status as defined by the current American Society of Clinical Oncology and College of American Pathologists guidelines at time of study entry.
• Locally advanced inoperable or metastatic MpBC with measurable disease by RECIST 1.1 Both first- and second-line patients will be eligible for this trial. Patients may have received prior immunotherapy, per standard of care.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate organ and marrow function as defined below:
‣ Hemoglobin ≥9.0 g/dl (without blood transfusion within 2 weeks of laboratory test used to determine eligibility)
⁃ Absolute neutrophil count ≥1000/μL (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility)
⁃ Platelet count ≥100,000/μL (without transfusion within 2 weeks of laboratory test used to determine eligibility)
⁃ Serum total bilirubin (TB) ≤1.5 x institutional upper limit of normal (ULN; In the case of known Gilbert's syndrome, a higher serum TB \[\>1.5 x ULN\] is allowed),
⁃ Aspartate transaminase/alanine transaminase ≤5 x institutional ULN
⁃ Creatinine ≤1.5X the ULN or measured creatinine clearance ≥ 60 mL/min/1.
• Fasting blood glucose of ≤140 mg/dl and HgbA1c ≤7.0.
• Ability to swallow oral medication.
⁃ Ability to take aspirin.
⁃ Women of childbearing potential must agree to use contraception for the duration of the study through 90 days after the last dose of study treatment. A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm during the study and up to the time period as specified in labels of study drugs.
⁃ If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting the study treatment.
⁃ Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations.