Description:
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
Title
- Brief Title: A Study to Evaluate the Potential Benefit of the Addition of BYL719 to Paclitaxel in the Treatment of Breast Cancer and Head-and-neck Cancer
- Official Title: A Phase Ib Open Label Dose Finding Study of BYL719 in Combination With Paclitaxel in Advanced Solid Tumors Followed by Two Expansion Phases in Locally Advanced/Metastatic Chemotherapy Naive HER2 Negative Breast Cancer Patients (HER2- mBC) and in Recurrent and Metastatic Head-and-neck Squamous Cell Carcinoma Patients (HNSCC) Pre-treated With Platinum Based Therapy
Clinical Trial IDs
- ORG STUDY ID:
CBYL719Z2101
- NCT ID:
NCT02051751
Conditions
- Neoplasms, Breast Neoplasms, Head and Neck Neoplasms
Interventions
Drug | Synonyms | Arms |
---|
BYL719 | | BYL719 and paclitaxel |
Paclitaxel | | BYL719 and paclitaxel |
Purpose
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
Trial Arms
Name | Type | Description | Interventions |
---|
BYL719 and paclitaxel | Experimental | All patients enrolled in the study will receive BYL719 once daily plus weekly paclitaxel | |
Eligibility Criteria
Inclusion criteria For entire trial:
1. - Adult > or = 18 years old
2. - has signed the Informed Consent Form (ICF)
3. - has at least one measurable or non-measurable disease as per RECIST 1.1
4. - has tumor tissue available for the analysis as described in the protocol
5. - has adequate bone marrow and organ function as defined in the protocol
6. - is able to swallow and retain oral medication for the dose escalation part, ALL
above PLUS
7. - has a histologically-confirmed, advanced unresectable solid tumors who have
progressed on standard therapy (or not been able to tolerate) within three months
before screening/baseline visit or for whom no standard anticancer therapy exists.
8. - has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 For dose
expansion part, patient has ALL of above first six criteria PLUS either: 9- has a
histologically/cytologically-confirmed HNSCC as detailed in the protocol and an ECOG
performance status ≤ 1 or:
- Patient is a Female with a histologically and/or cytologically confirmed
diagnosis of breast cancer as detailed in the protocol and an ECOG performance
status ≤ 1
Common exclusion criteria to Dose escalation and Dose expansion parts:
1. - has received previous treatment with a PI3K or AKT inhibitor as described in the
protocol
2. - has a known hypersensitivity to paclitaxel or other products containing Cremophor
3. - has a contraindication to use the standard pre-treatment for paclitaxel
4. - has a primary central nervous system (CNS) tumor or CNS tumor involvement as
detailed in the protocol
5. - has not recovered to grade 1 or better (except alopecia) from related side effects
of any prior antineoplastic therapy
6. - has received radiotherapy > or = 4 weeks prior to starting study drugs, with
exception of palliative radiotherapy, who has not recovered from side effects of such
therapy to baseline or Grade ≤ 1 and/or from whom ≥ 30% of the bone marrow was
irradiated
7. - has peripheral sensory neuropathy with functional impairment (CTC grade 2 neuropathy
or higher)
8. - has undergone major surgery ≤ 4 weeks prior to starting study treatment or who has
not recovered from side effects of such procedure
9. - has a clinically significant cardiac disease or impaired cardiac function as
detailed in the protocol
10. - is currently receiving medication with a known risk of prolonging the QT interval or
inducing Torsades de Pointes (TdP) and the treatment cannot either be discontinued or
switched to a different medication prior to starting study drug treatment
11. - has diabetes mellitus requiring insulin treatment and/or with clinical signs
12. - has impaired gastrointestinal (GI) function or GI disease as described in the
protocol
13. - has a known positive serology for human immunodeficiency virus (HIV), active
Hepatitis B, and/or active Hepatitis C infection
14. - has 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
15. - is currently receiving treatment with drugs known to be moderate or strong
inhibitors or inducers of isoenzymes CYP3A or CYP2C8 as detailed in the protocol
16. - is currently receiving treatment with agents that are metabolized solely by CYP3A
and/or have a narrow therapeutic window
17. - has a history of another malignancy within 2 years prior to starting study
treatment, except cured basal cell carcinoma of the skin or excised carcinoma in situ
of the cervix
18. - Patient has a history of non-compliance to medical regimen or inability to grant
consent
19. - Pregnant or nursing (lactating) women
20. - does not apply highly effective contraception during the study and through the
duration as defined in the protocol
For the HNSCC patient's cohort additional exclusion criteria are:
21- Treatment with more than one prior chemotherapy for recurrent/metastatic disease as
detailed in the protocol 22- Prior taxane treatment for metastatic disease additional
exclusion criteria for breast cancer patients' cohort:
- has received any prior cytotoxic therapy for the inoperable locally advanced (recurrent
or progressive) or metastatic disease, or who had a progression/recurrent disease within 6
months after completion of an adjuvant/neoadjuvant therapy as described in the protocol
Other protocol-defined inclusion/exclusion criteria may apply
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Dose escalation : Dose Limiting Toxicity (DLT) |
Time Frame: | Cycle 1 (28 days) |
Safety Issue: | |
Description: | 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. |
Secondary Outcome Measures
Measure: | Dose escalation:Number of patients with adverse events as a measure of safety and tolerability |
Time Frame: | Screening, every 28 days until 30 days after last dose |
Safety Issue: | |
Description: | type, intensity, severity and seriousness of adverse events according to the NCI CTC AE v4.03. Dose interruptions, reductions and dose intensity. |
Measure: | Dose escalation : BYL719 and Paclitaxel Plasma concentrations |
Time Frame: | Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 |
Safety Issue: | |
Description: | 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). |
Measure: | Dose expansion: Clinical benefit Rate in the breast cancer cohort |
Time Frame: | Baseline, every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years |
Safety Issue: | |
Description: | 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. |
Measure: | Dose expansion: Progression free survival |
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 |
Safety Issue: | |
Description: | Progression-free survival is defined as the time from start date of study treatment until objective tumor progression or death from any cause |
Measure: | Dose expansion: Overall response rate |
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 |
Safety Issue: | |
Description: | 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. |
Measure: | Dose expansion : Duration of Response |
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 |
Safety Issue: | |
Description: | 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. |
Measure: | Dose expansion: Plasma pharmacokinetics of BYL719 given in combination with paclitaxel in breast cancer and HNSCC patients |
Time Frame: | Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 15, and Day 1 of each subsequent Cycle |
Safety Issue: | |
Description: | Plasma concentration time profiles of BYL719 and appropriate individual PK parameters. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Completed |
Lead Sponsor: | Novartis Pharmaceuticals |
Trial Keywords
- Solid tumors, Head and neck non squamous cell carcinoma, breast cancer, PI3K inhibitor, BYL719, paclitaxel
Last Updated
December 8, 2020