| Eligibility |
Inclusion Criteria:
- Patients must have histologically confirmed squamous cell carcinoma of the head and
neck.
- Patients must be eligible for curative intent treatment with surgical resection
- Patients have measurable disease measuring 10 mm or more by clinical exam using
calipers according to RECIST 1.1 criteria. Caliper examination must be within 1 week
of registration.
- Patients are able to swallow and maintain oral medication
- Prior systemic therapy and/or radiotherapy are allowed if therapy was completed =12
weeks prior to BYL719 treatment start date.
- Age =18 years.
- Ability to understand and the willingness to sign a written informed consent document
and is able to comply with protocol requirements.
- ECOG performance status = 2 (Karnofsky =60%). See Appendix A.
- Life expectancy of greater than 6 months.
- Patients must have adequate organ and marrow function done within 2 weeks of starting
treatment as defined below:
1. Leukocytes = 3.0 x 109/L
2. Hemoglobin > 90 g/L
3. absolute neutrophil count =1.5 x 109/L
4. platelets = 100 x 109/L
5. total bilirubin = 1.5 x institutional upper limit of normal
6. AST(SGOT) and ALT(SGPT) = 2.5 x institutional upper limit of normal
7. creatinine = 1.5 x institutional upper limit of normal Or creatinine clearance =
60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
8. INR = 1.5
9. Random plasma glucose = 200 mg/dl or = 11.1 mmol/L
- Women of child-bearing potential must have a negative pregnancy test at screening and
agree to use a highly effective method of contraception (IUD or barrier method of
birth control or abstinence) during dosing and for 8 weeks after the final dose of
study treatment. Hormonal contraceptives may be affected by cytochrome P450 and are
therefore not considered effective for this study.
- Males must use a condom during intercourse while taking the study drug and for 4 weeks
after the final dose of study medication. In addition to avoiding potential risks to a
child conceived while on the study medication, a condom use will prevent delivery of
the study drug via seminal fluid.
- Study investigator has reviewed the patient's medication list and has taken
appropriate measures if the patient is taking any of the following:
1. Drugs known to be moderate or strong inhibitors or inducers of isoenzymes CYP34A
or CYP2C8
2. Drugs that are metabolized by CYP450 (CYP3A4, CYP3A5, CYP2C9 and CYP2C19)
3. BCRP inhibitors
4. Drugs that may alter gastrointestinal tract pH.
5. Medications with a known risk of prolonging QT interval or inducing Torsades de
Points (TdP)
6. Warfarin and coumadin derivates
7. Herbal medications
Exclusion Criteria:
- Patients with known distant metastatic disease
- Patients who have previously received BYL719 or have received any other
investigational agents within 30 days.
- Patients with diabetes mellitus requiring insulin or documented steroid induced
diabetes mellitus
- Impaired gastrointestinal (GI) function or GI disease that may significantly alter the
absorption of oral BYL719 (eg. ulcerative disease, uncontrolled nausea, vomiting,
diarrhea, malabsorption syndrome or small bowel resection).
- 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 has history of hypersensitivity to any drugs or metabolites or similar
chemical classes as BYL719
- Patient is currently receiving or has received systemic corticosteroids < 2 weeks
prior to starting treatment with BYL719, or has not fully recovered from side effects
of such treatment
- Patients who are currently receiving treatment with drugs known to be moderate or
strong inhibitors or inducers of isoenzymes CYP34A or CYP2C8. The patient must have
discontinued all such drugs at least 1 week before the start of study treatment.
Switching to a different medication prior to treatment start is allowed. Refer to
Appendix B for a list of strong and moderate CYP34A and CYP2CA inducers and
inhibitors.
Because the lists of these agents are constantly changing, it is important to regularly
consult a frequently-updated list such as
http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the
Physicians' Desk Reference may also provide this information
- Patient receiving medication with a known risk of prolonging the QT interval or
inducing Torsades de Pointes (TdP) and the treatment cannot be discontinued or
switched to a different medication prior to starting study treatment. Refer to
Appendix B, Table 2.
- 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
- Patients who have received live attenuated vaccines within 1 week of start of study
medication and during the study. Patient should also avoid close contact with others
who have received live attenuated vaccines. Examples of live attenuated vaccines
include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever,
varicella and TY21a typhoid vaccines.
- Uncontrolled intercurrent illness or medical conditions that would, in the treating
physician's judgment, contraindicate patient participation including, but not limited
to: active or uncontrolled infection, chronic active hepatitis, immune-compromised,
acute or chronic pancreatitis, uncontrolled high blood pressure, interstitial lung
disease, etc.)
- Patient has any of the following cardiac abnormalities:
1. History of documented congestive heart failure (New York Heart Association
functional classification III-IV), documented cardiomyopathy
2. known Left Ventricular Ejection Fraction (LVEF) < 50%
3. myocardial infarction < 6 months prior to enrollment
4. unstable angina pectoris
5. serious uncontrolled cardiac arrhythmia
6. symptomatic pericarditis
7. QTcF > 480 msec on the screening ECG (using the QTCF formula)
- Patients with known positive serology for human immunodeficiency virus (HIV).
HIV-positive patients on combination antiretroviral therapy are ineligible because of
the potential for pharmacokinetic interactions with BYL719. In addition, these
patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy.
- Patient who has not recovered to grade 1 or better (except alopecia, chronic stable
neuropathy or hearing impairment) from related side effects of any prior
antineoplastic therapy
- Patient who has undergone major surgery within 14 days prior to starting study
treatment or who has not recovered from side effects of such procedure.
- 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). Patients with elevated hCG at baseline that
is judged to be related to the tumor are eligible if hCG levels do not show the
expected doubling when repeated 5-7 days later, or pregnancy has been ruled out by
vaginal ultrasound.
- Patient who does not apply highly effective contraception during the treatment with
BYL719 and through the duration as defined below after the final dose of BYL719:
1. Sexually active males should use a condom during intercourse while taking drug
and for 4 weeks* after the final dose of alpelisib 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 female physiologically capable
of becoming pregnant, must use highly effective contraception during the IPP and
through at least 4 weeks* after the final dose of alpelisib
3. 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), total hysterectomy or tubal ligation at least six weeks before starting
treatment with alpelisib. 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 patients participating to this IPP, 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.
Note: Hormonal contraception methods (e.g. oral, injected, and implanted) are not allowed
as alpelisib BYL719 may decrease the effectiveness of hormonal contraceptives.
|
