Alpelisib in Treating Participants With Transorally Resectable HPV-Associated Stage I-IVA Oropharyngeal Cancer



Status:Recruiting
Healthy:No
Age Range:Any
Updated:12/19/2018
Start Date:December 14, 2018
End Date:December 31, 2022

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Biomarker Modulation by Alpelisib (BYL719) in Transorally Resectable, HPV-Associated HNSCC: A Phase II Window Trial

This phase II trial studies how well alpelisib works in treating participants with human
papillomavirus(HPV)-associated stage I-IVA head and neck cancer that can be removed by
surgery. Alpelisib may stop the growth of tumor cells by blocking some of the enzymes needed
for cell growth.

PRIMARY OBJECTIVES:

I. To assess the preliminary efficacy of neoadjuvant Alpelisib (BYL719) in patients with
transorally-resectable, HPV+ head and neck squamous cell carcinoma (HNSCC), as measured by
quantitative change in tumor size (change in T) following 14-21 days of treatment.

II. To evaluate the relationship between genomic PIK3CA activation to change in T.

SECONDARY OBJECTIVES:

I. To describe the tolerability of brief neoadjuvant exposure to BYL719. II. To assess the
effect of BYL719 on the tumoral Ki-67 proliferation index. III. To evaluate viral and
molecular mediators of response and resistance to BYL719, including viral messenger
ribonucleic acid (mRNA), E6 and E7 oncoproteins, and phosphorylated (p)HER3.

OUTLINE:

Participants receive Alpelisib orally (PO) once daily (QD) for 14-21 days in the absence of
disease progression of unacceptable toxicity and then undergo surgery. Participants may
receive Alpelisib for up to 28 days if surgery is delayed.

After completion of study treatment, participants are followed up for up to 12 weeks.

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 and planned for primary transoral resection and/or neck dissection

- Eastern Cooperative Oncology Group (ECOG) performance status 0-1

- 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

- Creatinine ? 1.5 x institutional upper limit of normal (ULN)

- Bilirubin ? 1.5 x ULN

- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ? 2.5 x ULN

- Ability to swallow and retain oral study medication, either as a whole tablet or a
drinkable suspension

- 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

- Poorly controlled diabetes mellitus

- Patients with type II diabetes who have either a fasting plasma glucose (FPG) of
? 140 or a hemoglobin A1C (HgBA1C) of ? 6.4 will be excluded; type 1 diabetic
patients will also be excluded

- Patient has any of the following cardiac abnormalities:

- Symptomatic congestive heart failure

- 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 enrollment

- Unstable angina pectoris

- Serious uncontrolled cardiac arrhythmia

- Symptomatic pericarditis

- 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 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 and must have discontinued strong inhibitors before the
start of treatment; switching to a different medication prior to randomization is
allowed

- 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 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 or a drinkable suspension,
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 such as infection requiring systemic
antibiotics or anti-fungals; chronic hepatitis; severely impaired lung function

- Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for
treatment of either a psychiatric or physical (e.g., infectious) illness
We found this trial at
1
site
Tucson, Arizona 85724
Principal Investigator: Julie E. Bauman
Phone: 520-626-4101
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mi
from
Tucson, AZ
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