Alpelisib in Treating Patients with Transorally Resectable HPV-Associated Stage I-IVA Oropharyngeal Cancer

Inclusion Criteria

• Cytologic or histologic diagnosis of oropharyngeal squamous cell carcinoma
• Clinical stage I-IVa p16+ oropharyngeal squamous cell carcinoma, based upon the American Joint Committee on Cancer (AJCC) staging manual, 7th edition
• No evidence of distant metastatic disease
• Carcinoma must be HPV-associated, which is defined as positive for p16 protein by immunohistochemistry (IHC); p16 positivity is defined as >= 70% of tumor cells demonstrating diffuse cytoplasmic and nuclear staining for p16 by immunohistochemistry in a Clinical Laboratory Improvement Amendments (CLIA) certified pathology lab; p16 testing is standard at University Advising and Career Center (UACC) and Tucson community sites, and may be conducted locally
• Appropriate candidate and planned for primary transoral resection and/or neck dissection
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 at time of consent
• Clinically or radiologically measurable disease; the primary tumor and/or neck nodes may be measurable according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (tumor diameter >= 1 cm; short-axis lymph node diameter >= 1.5 cm) OR by caliper measurement (tumor diameter >= 1 cm)
• Absolute neutrophil count (ANC) >= 1,500/ul (within 4 weeks of registration) * A redraw is permitted for screening within the 4 weeks
• Creatinine =< 1.5 x institutional upper limit of normal (ULN) (within 4 weeks of registration) * A redraw is permitted for screening within the 4 weeks
• Bilirubin =< 1.5 x ULN (within 4 weeks of registration) * A redraw is permitted for screening within the 4 weeks
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 x ULN (within 4 weeks of registration)
• Fasting serum amylase =< 2 x ULN (within 4 weeks of registration) * A redraw is permitted for screening within the 4 weeks
• Fasting serum lipase =< ULN (within 4 weeks of registration) * A redraw is permitted for screening within the 4 weeks
• Ability to swallow and retain oral study medication as a whole tablet
• Have signed written informed consent

Exclusion Criteria

• Subjects who fail to meet the above criteria
• Prior therapy for head and neck cancer is not allowed
• Patients with an established diagnosis of diabetes mellitus type I or not controlled type II
• Patient has a known hypersensitivity to alpelisib, or to any of the excipients of alpelisib
• Patient has currently documented pneumonitis (the chest computed tomography [CT] scan performed at baseline for the purpose of tumor assessment should be reviewed to confirm that there are no relevant pulmonary complications present)
• Patient has any of the following cardiac abnormalities: * Symptomatic congestive heart failure within 12 months prior to the start of study treatment * History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy * Left ventricular ejection fraction (LVEF) < 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) * Myocardial infarction =< 6 months prior to start of study treatment * Unstable angina pectoris * Serious uncontrolled cardiac arrhythmia * History of angina pectoris, coronary artery bypass graft (CABG), symptomatic pericarditis prior to the start of study treatment * Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mmHg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication. (initiation or adjustment of antihypertensive medication(s) is allowed during screening; hypertension must be controlled prior to administering the study drug.) * Fridericia's corrected QT (QTcF) > 480 msec on the screening electrocardiogram (ECG) (using the QTcF formula) currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting treatment with BYL719
• Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise; therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
• Patient is currently receiving any of the following medications and cannot be discontinued at least 7 days prior to the start of the treatment: * Medications that have a known risk to prolong the QT interval or induce Torsade de Pointes (TdP) * Herbal preparations/medications
• Patient is currently receiving treatment with drugs known to be moderate or strong inhibitors or inducers of isoenzyme CYP3A; the patient must have discontinued strong inducers for at least one week prior to the start of study treatment and must have discontinued strong inhibitors before the start of treatment; switching to a different medication prior to randomization is allowed
• History of acute pancreatitis within 1 year of screening or past medical history of chronic pancreatitis
• Patient with 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 a history of Stevens-Johnson-syndrome (SJS) or toxic epidermal necrolysis (TEN)
• Patient with known positive serology for human immunodeficiency virus (HIV)
• Patient with any other condition that would, in the investigator’s judgment, preclude patient’s participation in the clinical study due to safety concerns or compliance with clinical study procedures, e.g. infection/inflammation, intestinal obstruction, unable to swallow oral study medication as a whole tablet, social/psychological complications
• Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)
• Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment: * Sexually active males should use a condom during intercourse while taking BYL719 and for 16 weeks after the final dose of BYL719, and should not father a child in this period, but may be recommended to seek advice on conservation of sperm; a condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid; moreover, sexually active males should not father a child for 6 months after completion of radiation; per standard clinical practice * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraception during the study and through at least 12 weeks after the final dose of BYL719; moreover, per standard clinical practice, women should not become pregnant for 12 months after completion of radiation; highly effective contraception is defined as either: ** Total abstinence: When this is in line with the preferred and usual lifestyle of the subject; (periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception) ** Female sterilization: have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment; in case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment ** Male partner sterilization (with the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate); (for female study subjects, the vasectomized male partner should be the sole partner for that patient) ** Use a combination 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. *** Note: Hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed as BYL719 may decrease the effectiveness of hormonal contraceptives. ** NOTE: Women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) at least six weeks ago
• Severe and/or uncontrolled medical conditions
• Active systemic infection requiring systemic antibiotics or anti-fungals within 7 days prior to first dose of study drug * Note: Active topical infections (for example oral thrush) do not exclude a subject even if treated with systemic antibiotics or systemic antifungals
• Chronic hepatitis
• Severely impaired lung function
• Unresolved osteonecrosis of the jaw
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness