Dose escalation part:to determine the highest dose of BYL719 administered on a daily basis when given in combination with weekly paclitaxel Dose escalation part: to confirm the safety and tolerability of the BYL719 and paclitaxel combination
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
BYL719 will be administered orally once daily on a continuous dosing schedule and dosed on a flat-fixed dose and not adjusted by body weight or body surface area, starting on Day 2 in the dose escalation part and Day 1 in the dose expansion part. In the dose escalation part, the BYL719 starting dose will be 300mg, with anticipated dose escalation to 350mg. In the dose expansion part, BYL719 will be administered at the recommended dose determined in the dose escalation part.
Paclitaxel will be administered once weekly at a dose of 80 mg/m2 i.v. (days 1, 8, 15 and 22) in a 28 day cycle in both dose escalation and expansion.
Highlands Oncology Group
Fayetteville, Arkansas, United States
Horizon Oncology Center BioAdvance
Lafayette, Indiana, United States
Novartis Investigative Site
Toulouse, France
Novartis Investigative Site
Milan, MI, Italy
Dose escalation : Dose Limiting Toxicity (DLT)
A dose-limiting toxicity (DLT) is an adverse event or abnormal laboratory value assessed as being unrelated to disease, disease progression, inter-current illness, or concomitant medications, and that occurs within the first cycle of treatment with BYL719 plus paclitaxel and meets any of the pre-defined criteria.
Time frame: Cycle 1 (28 days)
Dose expansion : Number of patients with adverse events as a measure of safety and tolerability
type, intensity, severity and seriousness of adverse events according to the NCI CTC AE v4.03. Dose interruptions, reductions and dose intensity.
Time frame: Screening, every 28 days until 30 days after last dose
Dose escalation:Number of patients with adverse events as a measure of safety and tolerability
type, intensity, severity and seriousness of adverse events according to the NCI CTC AE v4.03. Dose interruptions, reductions and dose intensity.
Time frame: Screening, every 28 days until 30 days after last dose
Dose escalation : BYL719 and Paclitaxel Plasma concentrations
Plasma concentration time profiles of BYL719 and paclitaxel. Plasma PK parameters of paclitaxel (single agent vs. combination) and BYL719 (steady state in combination with paclitaxel).
Time frame: Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9
Dose expansion: Clinical benefit Rate in the breast cancer cohort
Clinical benefit rate is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) or stable disease (SD) for more than 24 weeks of duration of response.
Time frame: Baseline, every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years
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Novartis Investigative Site
Barcelona, Catalonia, Spain
Dose expansion: Progression free survival
Progression-free survival is defined as the time from start date of study treatment until objective tumor progression or death from any cause
Time frame: Baseline, every 6 weeks (head-and-neck squamous cell carcinoma (HNSCC) patients) or every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years
Dose expansion: Overall response rate
Overall response rate is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR), based on RECIST 1.1 criteria and the investigator assessment.
Time frame: Baseline, every 6 weeks (HNSCC patients) or every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years
Dose expansion : Duration of Response
Duration of response is defined as the time of first occurrence of CR or PR until the date of the first documented disease progression or death due to the disease.
Time frame: Baseline, every 6 weeks (HNSCC patients) or every 8 weeks (breast cancer patients) from start of treatment until first documented disease progression up to 2 years
Dose expansion: Plasma pharmacokinetics of BYL719 given in combination with paclitaxel in breast cancer and HNSCC patients
Plasma concentration time profiles of BYL719 and appropriate individual PK parameters.
Time frame: Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 15, and Day 1 of each subsequent Cycle