Clinical trial NCT01132625: Dose Escalation Study of AUY922 in Advanced Solid Malignancies in Japan
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: HSP90
molecular chaperone
advanced solid tumors
Japan
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-05-28
Enrollment: 37
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: establish maximum tolerate dose (safety and tolerability)
timeFrame: about 3 years
Secondary outcomes:
measure: Safety assessed by type, frequency and severity of adverse events
timeFrame: about 4 years
measure: Efficacy assessed by RECIST
timeFrame: about 4 years
measure: Pharmacokinetic assessed by Cmax, Tmax, AUC
timeFrame: about 3 years
measure: Pharmacodynamic assessed by blood and tumor biomarkers at baseline and post AUY922
timeFrame: about 4 years
Other outcomes:
Locations:
city: Kashiwa
country: Japan
facility: Novartis Investigative Site
state: Chiba
city: Sunto-gun
country: Japan
facility: Novartis Investigative Site
state: Shizuoka
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: