Adult female patients with HER2 positive locally advanced or metastatic breast cancer who received prior trastuzumab treatment. Phase II: patients must have additionally received prior taxane therapy and have trastuzumab resistant disease MedDRA version: 14.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: BEZ235
Product Code: BEZ235
Pharmaceutical Form: Powder for oral suspension
CAS Number: 1028385-32-1
Current Sponsor code: BEZ235
Concentration unit: mg milligram(s)
Concentration type:
Sponsors
Novartis Farmaceutica S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria applicable to Phase Ib and II: ? Patient is a female ? 18 years of age. ? Patient has a histologically and/or cytologically confirmed diagnosis of HER2-positive invasive breast cancer with inoperable locally advanced or metastatic disease ? Patients with controlled or asymptomatic CNS metastases are eligible ? Patient has adequate bone marrow and organ functions, and has recovery from all clinically significant toxicities related to prior anti-neoplastic therapies ? Absolute neutrophil count (ANC) ? 1.5 x 109/L ? Platelets ? 100 x 109/L ? Hemoglobin (Hgb) ? 9.0 g/dL ? INR ? 2 ? Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ? 3 x ULN (or ? 5.0 x ULN if liver metastases are present) ? Total serum bilirubin ? 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ? 3.0 x ULN, with direct bilirubin ? 1.5 x ULN) ? Serum creatinine ? 1.5 x ULN ? Fasting plasma glucose (FPG) ? 140mg/dL [7.8 mmol/L] ? HbA1c ? 8% ? Patient has received prior trastuzumab (alone or in combination) but NO more than 3 prior cytotoxic chemotherapy lines ? Prior endocrine and radiotherapy allowed ? Patient has ECOG performance status of 0-2 (Phase Ib) or 0-1 (Phase II) Additional criteria for Phase II: ? Available tumor tissue (/archival or fresh) for biomarker analysis; known PI3K activation status ? At least one measurable lesion as per RECIST 1.1 ? Patient has received prior treatment with a taxane ? Patient has ?trastuzumab-resistance disease? defined as: ? Recurrence while on trastuzumab (or T-DM1) or within 12 months since the last infusion in the adjuvant setting ? Progression while on or within 4 weeks since the last infusion of trastuzumab (or T-DM1) in the locally advanced or metastatic setting Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: Exclusion criteria applicable for Phase Ib and II: ? Previous treatment with PI3K and/or mTOR inhibitors ? Symptomatic/uncontrolled Central Nervous System (CNS) metastases ? Concurrent malignancy or malignancy in the last 3 years prior treatment ? Wide field radiotherapy ? 28 days or limited field radiation for palliation ? 14 days prior to starting study drug ? Active cardiac disease (e.g. LVEF less than institutional lower limit of normal, QTcF > 480 msec, unstable angina pectoris, ventricular, supraventricular or nodal arrhythmias) ? Inadequately controlled hypertension ? Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BEZ235 ? Treatment at start of study treatment with drugs with a known risk to induce Torsades de Pointes, moderate and strong inhibitors or inducers of isoenzyme CYP3A4, warfarin and coumadin analogues, LHRH agonists ? Intolerance or contraindications to trastuzumab treatment ? Pregnant or nursing (lactating) woman Additional exclusion criterion for Phase II: ? Prior treatment with capecitabine and lapatinib ? Intolerance or contraindications to capecitabine and lapatinib ? Previous treatment with HER-2 targeted agents other than trastuzumab or T-DM1 ? Peripheral neuropathy ? Grade 2 Other protocol-defined inclusion/exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase Ib: to determine the MTD and/or RP2D of BEZ235 in combination with trastuzumab Phase II: to estimate the treatment effect of BEZ235 plus trastuzumab versus capecitabine and lapatinib;Secondary Objective: Phase Ib: - to assess the preliminary efficacy of the study treatment - to evaluate safety of BEZ235 in combination with trastuzumab Phase II: - to estimate/compare the effect of study treatment - to evaluate the safety and tolerability of the study treatment;Primary end point(s): Phase Ib: DLTs (the first cycle) at each dose level Phase II: progression free survival (PFS);Timepoint(s) of evaluation of this end point: Phase Ib: first treatment cycle (28 days) Phase II: from start of treatment until disease progression | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase Ib: - frequency and severity of Adverse Events, - Progression Free Survival (PFS), Overall Response Rate (ORR), Clinical Benefit Rate (CBR) Phase II: - ORR, CBR - frequency and severity of Adverse Events;Timepoint(s) of evaluation of this end point: Phase Ib: - from randomization until disease progression - from randomization until 30d after treatment discontinuation Phase II: - from start of treatment until disease progression - from start of treatment until 30d after treatment discontinuation | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Czech Republic, France, Germany, Hong Kong, Hungary, Italy, Japan, Korea, Republic of, Netherlands, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, United Kingdom, United States
Contacts
Public ContactJavier Malpesa
Novartis Farmaceutica S.A:
Outcome results
None listed