| Eligibility |
Inclusion Criteria:
- Locally and/or regionally advanced (M0) head and neck squamous cell carcinoma (AJCC
Stage III-IVB), cytologically or pathologically confirmed by Department of Pathology
at MSKCC, for which curative-intent radiation therapy is planned.
- Age = 18 years
- ECOG Performance Status = 1
- Adequate organ function and laboratory parameters as defined by:
- Absolute neutrophil count = 1.0 x 109/L
- Hemoglobin = 9 g/dl
- Platelets = 100 x 109/L
- AST/SGOT and ALT/SGPT = 2.5X ULN (upper limit of normal)
- bilirubin = 1.5X ULN
- creatinine = 1.5X ULN
- Fasting glucose < 140 mg/dL
- Men and women of childbearing potential must be willing to consent to using effective
contraception while on treatment and for males at least 4 months thereafter and for
females at least 3 months thereafter.
- Negative serum pregnancy test (ß-hCG) within 72 hours before starting study treatment
for all women of childbearing potential.
- Able to understand and voluntarily sign the informed consent form, and able to comply
with the study visit schedule and other protocol requirements.
- Low risk for tumor lysis syndrome (TLS)
- Sexually active males must use a condom during intercourse while taking the drugs and
for 16 weeks after stopping treatment and should not father a child in this period. A
condom is required to be used also by vasectomized men in order to prevent delivery of
the drug via seminal fluid.
- Patient is able to swallow and retain oral medication
Exclusion Criteria:
- Any prior known radiation therapy in head and neck area
- Clinically significant cardiac disease or impaired cardiac function such as:
- Congestive heart failure (CHF) requiring treatment (New York Heart Association =
grade 2), Left Ventricular Ejection Fraction (LVEF) = 50% dose determined by
multi-gated acquisition (MUGA) scan or echocardiogram, or uncontrolled arterial
hypertension defined by blood pressure greater than 140/80 mmHg at rest (average
of 3 consecutive readings)
- History or current evidence of clinically significant cardiac arrhythmias, atrial
fibrillation and/or conduction abnormality, (e.g. congenital long QT syndrome,
high grade\complete AV blockage).
- Acute coronary syndrome (including myocardial infarction, unstable angina,
coronary artery bypass graft (CABG), for coronary angiography angioplasty and
stenting), < 3 months prior to screening
- QT interval adjusted according to Fredericia (QTcF) > 480 msec on screening EKG
- Patient with clinically manifest diabetes mellitus, or documented steroid induced
diabetes mellitus
- Patient with history of another malignancy within 2 years prior to starting study
treatment, except for cured basal cell carcinoma of the skin or excised carcinoma in
situ of the cervix
- Patient who has not recovered to grade 1 or better (except alopecia) from related side
effects of any prior antineoplastic therapy
- Patient who has had systemic therapy within 4 weeks (6 weeks for nitrosoureas or
mitomycin C) prior to study entry
- Patient who has undergone major surgery = 4 weeks prior to starting study treatment or
who has not recovered from side effects of such procedure
- 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,
social/psychological complications
- Impaired 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 who has participated in a prior therapeutic investigational drug study within
30 days prior to enrollment
- 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 treatment with drugs known to be strong inhibitors or
inducers of isoenzyme CYP3A. The patient must have discontinued strong inducers for at
least one week and must have discontinued strong inhibitors before the start of
treatment. Switching to a different medication prior to the start of treatment is
allowed; (Refer to Appendix 2).
- Known positive serology for human immunodeficiency virus (HIV), active hepatitis B,
and/or active hepatitis C infection
- Patient has a known hypersensitivity to any of the excipients of BYL719
- Patient has a known hypersensitivity to cetuximab or any other monoclonal antibody
- Patient has a known history of non-compliance to medical regimen or inability to grant
consent
- Pregnant 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)
- Women 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:
a. Sexually active males should use a condom during intercourse while taking drug and
for 16 weeks after the final dose of study treatment 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 b. 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 16 weeks after the final dose of study
treatment. 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 a+b):
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.
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.
- Patients with nasopharyngeal carcinoma are not eligible.
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