A phase Ib multi-center, open-label, 4-arm dose-escalation study of oral BEZ235 and BKM120 in combination with weekly paclitaxel in patients with advanced solid tumors and weekly paclitaxel/trastuzumab in patients with HER2+ metastatic breast cancer.
- Conditions
- advanced solid tumorsHER2-positive Breast Cancer1002765510006232
- Registration Number
- NL-OMON34229
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 5
Dual-agent part:
• Patients with metastatic or locally advanced solid tumors eligible for weekly paclitaxel;Triple-agent part:
• HER2+ metastatic or locally advanced breast cancer patients eligible for weekly paclitaxel and trastuzumab;For both parts:
• WHO performance status <= 2
• Absolute neutrophil count >= 1.5 ×109/L
• Hemoglobin >= 10g/dL = 6.2 mmol/L
• Platelets >= 100 ×109/L
• Serum albumin >= 3.0 g/dL
• AST/SGOT and ALT/SGPT <= upper limit of normal (ULN) or <=2.5 × ULN if liver metastases are present
• Serum bilirubin <= ULN or <= 1.5 ×ULN if liver metastases are present
• Serum creatinine <= 1.5 × ULN or 24-hour creatinine clearance >= 50 mL/min
• Partial thromboplastin time (PTT) <= 1.5 × ULN
• Prothrombin time (PT)/international normalized ratio (INR) <=1.5 × ULN
• New York Heart Association (NYHA) grade <= 2
• Left ventricular ejection fraction (LVEF) >= 50% (MUGA scan or echocardiogram)
• QTc interval <= 460 ms on screening ECG
• Fasting plasma glucose <= 140 mg/dL (7.8 mmol/L)
• Recovery from all reversible adverse events of previous anticancer therapies to grade 1, except for alopecia and peripheral neuropathy
• Patients with primary central nervous system (CNS) tumor or CNS tumor involvement. However, patients with a metastatic CNS lesion may participate in this trial, if the patient is > 4 weeks from therapy completion, clinically stable and not receiving enzyme-inducing antiepileptic drugs or corticosteroid therapy
• Patients who have received prior systemic anticancer therapy within the following time frames
- Chemotherapy <= 3 weeks before study treatment (6 weeks for nitrosoureas)
- Biological therapy <= 4 weeks before study treatment, except trastuzumab
- Investigational drug <= 4 weeks before study treatment
• Major surgery <= 4 weeks before study treatment
• Chronic treatment with corticosteroids or other immunosuppressive agents
• Uncontrolled diabetes mellitus
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug
• Treatment with agents that are metabolized solely by CYP3A and/or have a narrow therapeutic window or are strong inhibitors or inducers of CYP3A or CYP2C8.
• QT-prolonging medication known to have a risk to induce Torsades de Pointes
• Radiotherapy <= 4 weeks before starting study drug
• Prior treatment with PI3K inhibitors
• Known hypersensitivity to paclitaxel, polyethoxylated castor oil (Cremophor EL) or excipients of trastuzumab, BEZ235, or BKM120
• Patients with known human immunodeficiency virus (HIV)
• Active or history of major depressive episode, bipolar disorder, obsessive -compulsive disorder, schizophrenia, history of suicide attempt or ideation, or homicide
• Women of child-bearing potential and male patients must use adequate contraception methods throughout the study and for 12 weeks after study drug discontinuation
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Incidence of dose-limiting toxicities (DLTs) in patients with concomitant<br /><br>administration of BEZ235 or BKM120 and paclitaxel (± trastuzumab).</p><br>
- Secondary Outcome Measures
Name Time Method