Clinical Trials /

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

NCT02051751

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

Related Conditions:
  • Breast Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
BYL719BYL719 and paclitaxel
PaclitaxelBYL719 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

NameTypeDescriptionInterventions
BYL719 and paclitaxelExperimentalAll patients enrolled in the study will receive BYL719 once daily plus weekly paclitaxel
  • BYL719
  • 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

April 5, 2017