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. - ND

• Conditions: Patients with advanced gastric cancer who have progressed after one line of chemotherapy.; MedDRA version: 9.1Level: PTClassification code 10017758

• Registration Number: EUCTR2009-015407-47-IT
• Lead Sponsor: OVARTIS FARMA

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-04-23
• Last Update Posted: 24 April 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1) Patients with cytological or histological confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma 2) Patients with progressive disease (radiological confirmation required) after one line of chemotherapy for advanced gastric cancer. In addition, patients may have also received prior adjuvant if recurrence occurred ≥6 months after adjuvant therapy completion 3) Patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression 4) Patients who meet the following criteria will be eligible for PET assessments: - At least one lesion must be measurable ( >2cm) - To be eligible for follow-up scans, patients should have uptake of the tracer in at least one lesion where the tumor-muscle ratio is >2 - Able to lie still and flat on the PET table 5) Age ≥ 18 years or age of consent in country of residence 6) Able to sign Informed Consent 7) World Health Organization (WHO) Performance Status of ≤ 1 8) Life expectancy of ≥ 12 weeks Patients must have the following laboratory values: 9) Hematologic: - Absolute Neutrophil Count (ANC) ≥1.5x109/L - Hemoglobin (Hgb) ≥ 9 g/dl - Platelets (plt) ≥100x109/L 10) Biochemistry: - Potassium within normal limits - Total calcium (corrected for serum albumin) and Phosphorus within normal limits - Magnesium above LLN or correctable with supplements - Adequate liver function defined as: AST/SGOT and ALT/SGPT ≤ 1.5 x Upper Limit of Normal (ULN) if AP > 2.5 ULN AST/SGOT and ALT/SGPT ≤ 2.5 x Upper Limit of Normal (ULN) if AP ≤ 5.0 x ULN if liver metastases are present Serum bilirubin ≤ 1.5 x ULN Serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 ml/min 11) Negative serum pregnancy test. The serum pregnancy test must be obtained prior to the first administration of study medication (≤ 72 hours prior to dosing) in all pre-menopausal women and women <2 years after the onset of menopause.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1)Patients with CNS metastasis which are: Symptomatic or Require treatment for symptom control and/or Growing Note: Patients without clinical signs or symptoms of CNS involvement are not required to have a CT/MRI of the brain 2)Prior treatment with any HSP90 or HDAC inhibitor compounds 3)Patients who received systemic anti-cancer treatment prior to the first dose of study medication within the following time frames: Radiotherapy, conventional chemotherapy: within 4 weeks Monoclonal antibodies such as Trastuzumab treatment within 4 weeks Palliative radiotherapy: within 2 weeks Nitrosoureas and mitomycin: within 6 weeks Any continuous dosing (i.e. daily dosing, every-other-day dosing, Monday- Wednesday-Friday dosing, weekly etc) of systemic anti-cancer treatment for which the recovery period is not known, or investigational drugs (i.e. targeted agents) within a duration of ≤5 half lives of the agent and their active metabolites (if any) 5)Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted) 6)Known sensitivity to taxanes, drugs formulated with polysorbate 80, or patients with Acute Myeloid Leukemia 7)Concomitant use of agents that induce, inhibit or are metabolized by CYP3A4, neuromuscular blocking agents and Atazanavir sulfate 8)Unresolved diarrhea ≥ CTCAE grade 1 9)Patients with malignant ascites that require invasive treatment 10)Patients who do not have either an archival tumor sample available or are unwilling to have a fresh tumor sample collected at baseline 11)Pregnant or lactating women 12)Fertile women of childbearing potential (WCBP) not using double-barrier methods of contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile). Male patients whose partners are WCBP not using double-barrier methods of contraception. 13)Patients with acute or chronic liver or renal disease 14)Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol. 15)Major surgery ≤ 2 weeks prior to randomization or who have not recovered from such therapy 16)Impaired cardiac function , including any one of the following: History (or family history) of long QT syndrome Mean QTc ≥ 450 msec on baseline ECG History of clinically manifested 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 or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, history of labile hypertension, or history of poor compliance with an antihypertensive regimen) Clinically significant resting bradycardia (< 50 beats per minute) Patients who are currently receiving treatment with any medication which has a relative risk of prolonging the QTcF interval or inducing Torsades de Pointes and cannot be discontinued or switched to an alternative drug prior to commencing start of treatment. Obligate use of a cardiac pacemaker 17)Known diagnosis of HIV infection (HIV testing is not mandatory) 18)Patients with a his

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the treatment effect on progression-free survival (PFS) in patients who receive AUY922 on a once weekly schedule versus patients who receive docetaxel or irinotecan.;Secondary Objective: Key secondary objective: to estimate the overall survival treatment effect and other time-related endpoints. Additional secondary objectives: - to estimate the objective response rate (ORR), to evaluate safety (based on CTCAE Version 3.0) and tolerability, and to characterize the pharmacokinetics (PK) of AUY922 patients in both Asian and Caucasian populations where feasible.;Primary end point(s): Progression-free survival (PFS): Progression-free survival (PFS) is the time from the date of randomization to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, PFS is censored at the date of last adequate tumor assessment.