A Window of Opportunity Study to Assess the Modulation of Biomarkers in Head and Neck Squamous Cell Cancer (HNSCC) By Preoperative Treatment With BYL719

NCT03138070 | Completed

• 1 other identifier: Window of Opportunity
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Single centre, single arm, preoperative window of opportunity study with a biomarker endpoint (expression profiling by RNA sequencing). Patients with resectable, histologically confirmed head and neck squamous cell carcinoma (HNSCC) for whom surgical treatment is planned as definitive management will be eligible.

Conditions

Head and Neck Squamous Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Phospho-S6 (235/6) Expression

  Phospho-S6 (235/6) measured at baseline from the biopsy tissue sample will be compared to the value measured following BYL719 treatment taken from the tissue removed at surgery using a paired t-test.

  Measured at baseline and at surgery

Secondary Outcomes (3)

• Phospho-AKT Levels (Ser473)

  Measured at baseline and at surgery

• Ki-67 Levels

  Measured at baseline and at surgery

• Severity of Adverse Events

  At baseline and within 14 days of last dose

Study Arms (1)

Arm 1

EXPERIMENTAL

14 days of BYL719 treatment, open label

Drug: BYL719

Interventions

BYL719 DRUG

BYL719 400 mg daily by mouth continue for 14 days

Also known as: Alpelisib

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Leukocytes ≥ 3.0 x 109/L
• Hemoglobin \> 90 g/L
• absolute neutrophil count ≥1.5 x 109/L
• platelets ≥ 100 x 109/L
• total bilirubin ≤ 1.5 x institutional upper limit of normal

You may not qualify if:

• 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:
• History of documented congestive heart failure (New York Heart Association functional classification III-IV), documented cardiomyopathy

Sponsors & Collaborators

• London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's: lead

Study Sites (1)

London Health Sciences Centre, London Regional Cancer Program

London, Ontario, N6A 4L6, Canada

Location

Related Publications (1)

• Ruicci KM, Meens J, Sun RX, Rizzo G, Pinto N, Yoo J, Fung K, MacNeil D, Mymryk JS, Barrett JW, Boutros PC, Ailles L, Nichols AC. A controlled trial of HNSCC patient-derived xenografts reveals broad efficacy of PI3Kalpha inhibition in controlling tumor growth. Int J Cancer. 2019 Oct 15;145(8):2100-2106. doi: 10.1002/ijc.32009. Epub 2018 Dec 18.

  PMID: 30468243 DERIVED

MeSH Terms

Interventions

Alpelisib

Study Officials

• Anthony Nichols

  London Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 25, 2017
• First Posted: May 3, 2017
• Study Start: October 20, 2017
• Primary Completion: September 13, 2021
• Study Completion: November 26, 2025
• Last Updated: January 28, 2026

Record last verified: 2024-09

Locations

CA (1)