A Window of Opportunity Study to Assess the Modulation of Biomarkers in Head and Neck Squamous Cell Cancer (HNSCC) By Preoperative Treatment With BYL719
Overview
- Phase
- Not Applicable
- Intervention
- BYL719
- Conditions
- Head and Neck Squamous Cell Cancer
- Sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Enrollment
- 15
- Locations
- 1
- Primary Endpoint
- Phospho-S6 (235/6) Expression
- Status
- Completed
- Last Updated
- 3 months ago
Overview
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.
Detailed Description
This is a 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. The median time from consultation to major head and neck surgery at our institution is 3.2 +/- 2.0 weeks (1 standard deviation). To provide the maximal opportunity to achieve a biomarker response and potentially observe clinical responses, patients will receive BYL719 orally daily at the maximum tolerated dose (400 mg/day) for 14 days. All patients will receive surgery as the standard of care. The gene expression profile, including Ki-67, from the surgical specimen and mandatory baseline tumor biopsy will be evaluated for primary and secondary pharmacodynamic endpoints.
Investigators
Eligibility Criteria
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:
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 CYP2C
- •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
Arms & Interventions
Arm 1
14 days of BYL719 treatment, open label
Intervention: BYL719
Outcomes
Primary Outcomes
Phospho-S6 (235/6) Expression
Time Frame: Measured at baseline and at surgery
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.
Secondary Outcomes
- Phospho-AKT Levels (Ser473)(Measured at baseline and at surgery)
- Severity of Adverse Events(At baseline and within 14 days of last dose)
- Ki-67 Levels(Measured at baseline and at surgery)