A randomized, open-label, multi-center phase II study to compare AUY922 with docetaxel or irinotecan in adult patients with advanced gastric cancer, who have progressed after one line of chemotherapy

- Patients with cytological or histological confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
- Patients with progressive disease (radiological confirmed) after one line of chemotherapy for advanced gastric cancer.
- At least one measurable lesion as defined by RECIST.
- Patients who meet the following criteria will be eligible for PET assessments:
o At least one lesion must be measurable ( >2cm)
o Able to lie still and flat on the PET table.
- WHO Performance Status of < 1
- Life expectancy of > 12 weeks
- Patients must have the following laboratory values:
o Absolute Neutrophil Count *1.5x109/L
o Hemoglobin * 9 g/dl <= 5.58 mmol/l
o Platelets *100x109/L
o Potassium, total calcium (corrected for serum albumin) and phosphorus within normal limits
o Magnesium above LLN
o Adequate liver function defined as:
AST/SGOT and ALT/SGPT * 1.5 x Upper Limit of Normal if Alkaline Phosphatase > 2.5 ULN or
AST/SGOT and ALT/SGPT * 2.5 x Upper Limit of Normal (ULN) if Alkaline Phopaphatse * 5.0 x ULN if liver metastases are present
o Serum bilirubin * 1.5 x ULN
o Serum creatinine * 1.5 x ULN or 24-hour clearance * 50 ml/min.
o Negative serum pregnancy test.

- Patients with CNS metastasis which are symptomatic or require treatment for symptom control and/or gowing.
- Prior treatment with any HSP90 or HDAC inhibitor
- Systemic anti-cancer treatment prior to the first dose of studymedication within the following timeframes:
o Radiotherapy, conventional chemotherapy and monoclonal antibodies, such as trastuzumab: within 4 weeks
o Palliative radiotherapy: within 2 weeks
o Nitrosoureas, mitomycin: within 6 weeks
o Any continuous-dosing of systemic anti-cancer therapiefor 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)
- Treatment with therapeutic doses of coumarin-type anticoagulants. Maximum daily dose of 2mg allowed.
- Known sensitivity to taxanes, drugs formulated with polusorbate 80 or patients with Acute Myeloid Leukemia.
- Concomitant use of agents that induce, inhibit or are metabolized by CYP3A4, neuromuscular blocking agenst and Atazanavir sulfate.
- Unresolved diarrhea * CTCAE grade 1
- Patients with malignant ascites that requires invasive treatment.
- No archival tumor sample available or unwilling to have a fresh tumor sample collected at baseline.
- Acute or chronic liver or renal disease.
- Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol.
- Impaired cardiac function, including any one of the following:
o History (or family history) of long QT syndrome.
o QTc * 450 msec on screening ECG.
o Clinically manifested ischemic heart disease * 6 months prior to study start.
o History of heart failure or left ventricular (LV) dysfunction (LVEF * 45%) by MUGA or ECHO.
o Clinically significant ECG abnormalities.
o History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes.
o Other clinically significant heart disease (e.g congestive heart failure, uncontrolled hypertension)
o Clinically significant resting bradycardia (< 50 beats per minute).
o Treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes.
o Cardiac pacemaker
- Known diagnosis of HIV infection
- history of another primary malignancy that is currently clinically significant or currently requires active intervention.