Dose Escalation Study of AUY922 in Advanced Solid Malignancies in Japan

Study Overview
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Brief Summary
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This study will characterize the safety, tolerability, efficacy, pharmacokinetics, and pharmacodynamics of AUY922 in adult patients with advanced solid malignancies in Japan.

Official Title
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A Japanese Phase I, Multi-center, Open-label, Study of AUY922 Administered Intravenously on a Once Weekly Schedule in Adult Patients With Advanced Solid Malignancies

Conditions
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Advanced Solid Tumors

Intervention / Treatment
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* Drug: AUY922


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with advanced malignant solid tumors ECOG Performance Status of ≤ 2 Patients must have the following laboratory values: Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Hemoglobin (Hgb) ≥ 8.5 g/dl, Platelets (plt) ≥ 100 x 109/L Potassium, Calcium, Magnesium, Phosphorus within normal limits or correctable with supplements AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) Serum bilirubin ≤ 1.5 x ULN, Serum albumin > 2.5g/dl, Serum creatinine≤ 1.5 x ULN or 24-hour clearance ≥ 50 ml/min Able to sign informed consent and to comply with the protocol Exclusion Criteria: Patients with brain metastasis. Prior treatment with any HSP90 or HDAC inhibitor compound. Treatment with therapeutic doses of coumarin anticoagulants. Pregnant and lactating women. Severe and/or uncontrolled acute or chronic liver disease Severe and/or uncontrolled acute or chronic renal disease Chronically significant heart disease History (or family history) of long QT syndrome. QTc ≥ 450 msec on screening ECG, ischemic heart disease, heart fail, ECG abnormalities, atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes. Patients who are currently receiving treatment with any medication which has a relative risk or prolonging the QTcF interval or inducing Torsades de Pointes Patients with known disorders due to a deficiency in bilirubin glucuronidation (e.g Gilbert's syndrome). Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AUY922<br> | Drug: AUY922<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| establish maximum tolerate dose (safety and tolerability) |  | about 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessed by type, frequency and severity of adverse events |  | about 4 years | 
| Efficacy assessed by RECIST |  | about 4 years | 
| Pharmacokinetic assessed by Cmax, Tmax, AUC |  | about 3 years | 
| Pharmacodynamic assessed by blood and tumor biomarkers at baseline and post AUY922 |  | about 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HSP90, molecular chaperone, advanced solid tumors, Japan