Dose Escalation Study of AUY922 in Advanced Solid Malignancies in Japan

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT01132625

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

18.5

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Advanced Solid Tumors	Drug: AUY922	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

37 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2008

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AUY922	Drug: AUY922

Arm

Intervention/Treatment

Experimental: AUY922

Drug: AUY922

Outcome Measures

Primary Outcome Measures

establish maximum tolerate dose (safety and tolerability) [about 3 years]

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).