| Eligibility |
Inclusion Criteria:
1. Cytologic or histologic diagnosis of p16+ squamous cell carcinoma of oropharyngeal or
unknown primary metastatic to the cervical met.
2. p16 positivity is defined as =70% of tumor cells demonstrating diffuse cytoplasmic and
nuclear staining for p16 by immunohistochemistry in a CLIA certified pathology lab.
3. Clinical stage I-IVa p16+ oropharyngeal squamous cell carcinoma, based upon the AJCC
staging manual, 7th edition.
4. No evidence of distant metastatic disease.
5. Appropriate candidate and planned for primary transoral resection and/or neck
dissection.
6. ECOG performance status 0-1 at time of consent.
7. Clinically or radiologically measurable disease; the primary tumor and/or neck nodes
may be measurable according to RECIST 1.1(tumor diameter = 1 cm; short-axis lymph node
diameter = 1.5 cm) OR by caliper measurement (tumor diameter = 1 cm).
8. Adequate hematologic, renal and hepatic function within 4 weeks of registration, as
defined by:
a) Absolute neutrophil count (ANC) = 1,500/ul b) Creatinine = 1.5 x institutional
upper limit of normal (ULN). c) Bilirubin = 1.5 x ULN, d) AST or ALT = 2.5 x ULN. e)
Fasting Serum amylase = 2 × ULN f) Fasting Serum lipase = ULN
Note: A redraw is permitted within the 4 weeks for screening purposes.
9. Ability to swallow and retain oral study medication as a whole tablet
10. Have signed the written informed consent
Exclusion Criteria:
1. Prior therapy for head and neck cancer is not allowed.
2. Established diagnosis of diabetes mellitus type I or not controlled type II.
3. Known hypersensitivity to alpelisib, or to any of the excipients of alpelisib.
4. Currently documented pneumonitis (Note: The chest CT scan performed at baseline for
the purpose of tumor assessment should be reviewed to confirm that there are no
relevant pulmonary complications present).
5. Any of the following cardiac abnormalities:
1. Symptomatic congestive heart failure within 12 months prior to the start of study
treatment
2. History of documented congestive heart failure (New York Heart Association
functional classification III-IV), documented cardiomyopathy
3. Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated
acquisition (MUGA) scan or echocardiogram (ECHO).
4. Myocardial infarction = 6 months prior to start of study treatment
5. Unstable angina pectoris
6. Serious uncontrolled cardiac arrhythmia
7. History of angina pectoris, coronary artery bypass graft (CABG), symptomatic
pericarditis prior to the start of study treatment
8. 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.) QTcF > 480 msec on the screening ECG (using the
QTcF formula)
6. 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.
7. Currently receiving any of the following medications and cannot be discontinued at
least 7 days prior to the start of the treatment:
1. Medications that have a known risk to prolong the QT interval or induce Torsade
de Pointes (TdP) and the treatment cannot be discontinued or switched to a
different medication prior to starting treatment with BYL719 (refer to list of
prohibited QT prolonging drugs provided in in Appendix 3)
2. Herbal preparations/medications
8. 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; (Refer to Appendix 2 and 3, Tables 1 and 2) for permitted
and non-permitted medications).
9. History of acute pancreatitis within1 year of screening or past medical history of
chronic pancreatitis
10. 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)
11. History of Stevens-Johnson-Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN).
12. Known positive serology for human immunodeficiency virus (HIV)
13. Any other condition, including severe and/or uncontrolled medical conditions, 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
14. Currently taking herbal preparations/medications and dietary supplements (except for
vitamins) and unwilling to stop.
15. 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 hCG laboratory test (> 5 mIU/mL)
16. 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:
1. Sexually active males must use a condom during intercourse while taking BYL719
and for 1 week 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.
2. 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 1 week after the final dose of BYL719. Highly effective
contraception is defined as either:
i. 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].
ii. 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 iii. 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] iv.
Use a combination of the following (both 1+2):
1. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
2. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault
caps) with spermicidal foam/gel/film/cream/vaginal suppository.
3. 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.
17. 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.
18. Chronic hepatitis
19. Severely impaired lung function
20. Unresolved osteonecrosis of the jaw
21. Prisoners or individuals who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness.
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