Solid tumors and metastatic breastcancer
Conditions
Interventions
AUY922 administered intravenously, once weekly as single agent.
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Breast cancer phase II expansion arms only 1a. Female patients with ER positive HER2 positive locally advanced non-operable metastatic breast cancer with history of trastuzumab resistance 1b. Female patients with ER positive non-operable locally advanced or metastatic breast cancer who received endocrine therapy and whose disease has progressed on at least one line of endocrine therapy for advanced disease. 2. At least one measurable lesion as defined by RECIST. 3. All patients must have progressive disease before entering to the study. 4. (WHO) Performance Status of * 2. 5. Life expectancy of * 12 weeks. 6. Patients must have the following laboratory values: * Absolute Neutrophil Count (ANC) * 1.5 x 109/L * Hemoglobin (Hgb) * 9 g/dl * Platelets (plt) * 100 x 109/L * Potassium, calcium, magnesium and phosphorus within normal limits or correctable with supplements * Liverfunctiontests * 2.5 x Upper Limit of Normal (ULN) or * 5.0 x ULN if liver metastases are present * bilirubin and creatinin * 1.5 x ULN or 24-hour clearance * 50 ml/min * albumin * 2.5g/dl
Exclusion criteria
Exclusion criteria: Main Exclusion criteria 1. CNS metastasis. 2. Prior treatment with any HSP90 or HDAC inhibitor compound. 3a. Radiotherapy within 4 weeks or palliative radiotherapy within 2 weeks 3b. Nitrosoureas, mitomycin and monoclonal antibodies, such as trastuzumab: within 6 weeks 3c. Systemic anticancer treatment for which the recovery period is not known, or investigational drugs within a duration of * 5 half lives of the agent and their active metabolites (if any) 4. Patients who have not recovered from side effects of previous systemic anticancer therapy to less than grade 2 prior to the first dose of study treatment 5. Treatment with therapeutic doses of sodium warfarin (Coumadin). Low doses of Coumadin (e.g. * 2mg/day for line patency) are permitted. 6. Patients using medications that are substrates, inhibitors or inducers of CYP3A4, CYP2C8, CYP2C9 and CYP2C19 and cannot be switched or discontinued to an alternative drug prior to commencing AUY922 dosing 7. Unresolved diarrhea * CTCAE grade 2. 8. Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline. 9. Acute or chronic liver disease. 10. Acute or chronic renal disease. 11. Other concurrent severe and/or uncontrolled medical conditions 12. Clinical significant cardiac disease e.g: * History of long QT syndrome or Mean QTc * 450 msec * History of clinically manifest ischemic heart disease * 6 months prior to study start. * History of heart failure or left ventricular (LV) dysfunction (LVEF * 45%) by MUGA or ECHO. * Clinically significant ECG abnormalities * History of atrial fibrillation, atrial flutter or ventricular arrhythmias * Clinically significant resting bradycardia (
Design outcomes
Secondary
| Measure | Time frame |
|---|---|
| * Safety: Type, frequency and severity of adverse events (CTCAE Version 3.0) * Efficacy: In the dose-escalation arm response will be also assessed by RECIST. * PK: Cmax, Tmax, AUC0-24 and AUC0-T * PD: PET response, blood and tumor biomarkers at baseline and post-AUY922 dosing. | — |
Primary
| Measure | Time frame |
|---|---|
| Phase I: to determine the MTD of AUY922 as a single agent, administered once weekly. Estimation of the MTD will be based upon the estimation of the probability of DLT in cycle 1. Phase II only (breast cancer) Efficacy: responders (CR/PR), non-responders with stable disease for at least 6 months (SD * 6 months), progressive disease within 6 months from study start or others | — |
Countries
Netherlands
Outcome results
None listed