Neoplasms, Breast Neoplasms, Head and Neck Neoplasms Clinical Trial
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
| Verified date | December 2020 |
| Source | Novartis |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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
| Status | Completed |
| Enrollment | 19 |
| Est. completion date | August 19, 2016 |
| Est. primary completion date | August 19, 2016 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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 |
| Country | Name | City | State |
|---|---|---|---|
| France | Novartis Investigative Site | Toulouse Cedex 9 | |
| Italy | Novartis Investigative Site | Milano | MI |
| Spain | Novartis Investigative Site | Barcelona | Catalunya |
| United States | Highlands Oncology Group | Fayetteville | Arkansas |
| United States | Horizon Oncology Center BioAdvance | Lafayette | Indiana |
| Lead Sponsor | Collaborator |
|---|---|
| Novartis Pharmaceuticals |
United States, France, Italy, Spain,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | 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. | Cycle 1 (28 days) | |
| Primary | 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. | Screening, every 28 days until 30 days after last dose | |
| Secondary | 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. | Screening, every 28 days until 30 days after last dose | |
| Secondary | 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). | Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9 | |
| Secondary | 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. | Baseline, every 8 weeks (Breast cancer patients) from start of treatment until first documented disease progression up to 2 years | |
| Secondary | 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 | 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 | |
| Secondary | 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. | 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 | |
| Secondary | 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. | 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 | |
| Secondary | 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. | Cycle 1 Day 1, Cycle 1 Day 8, Cycle 2 Day 15, and Day 1 of each subsequent Cycle |