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

Conditions: Neoplasms, Breast Neoplasms, Head and Neck Neoplasms

Summary: 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


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

Keywords: solid tumors, head and neck non squamous cell carcinoma, breast cancer, pi3k inhibitor, byl719, paclitaxel