?A phase II study to evaluate the efficacy and safety of the investigational compound AUY922 in combination with trastuzumab as second-line treatment in patients with HER2-positive advanced gastric cancer

Conditions: Patients with documented advanced HER2 positive gastric cancer progressing after clinical benefit to 1st line treatment with trastuzumab containing treatment. Clinical benefit is defined as overall response or stable disease of at least 12 weeks, from start of the 1st line therapy with trastuzumab as per RECIST.
MedDRA version: 14.1Level: PTClassification code 10063916Term: Metastatic gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2011-002570-23-IT

Lead Sponsor: OVARTIS FARMA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 48

Inclusion Criteria

1. Written informed consent obtained prior to any screening procedures 2. Patients with documented cytological or histological confirmed gastric adenocarcinoma or gastro-esophageal junction adenocarcinoma and proven HER2 positive. 3. Patients with progressive disease (radiological confirmation required according to RECIST) after first line of trastuzumab in combination with chemotherapy for advanced gastric cancer. 4. Age = 18 years or age of consent in country of residence and able to sign Informed Consent 5. ECOG performance status of 0-1 at study entry 6. HER2-overexpressing positive gastric tumor by IHC3+or IHC2+ with positive in situ hybridization 7. Measurable disease according to RECIST (Irradiated lesions can not be considered measurable unless they have clearly progressed since radiotherapy). 8. Negative serum pregnancy test. The serum pregnancy test must be obtained prior to any drug administration (= 72 hours prior to dosing) in all pre-menopausal women and for women < 2 years after the onset of menopause. 9. Patients must have the following laboratory values: Hematologic • Absolute Neutrophil Count (ANC) =1.5x109/L, • Hemoglobin (Hgb) = 9 g/dL, • Platelets (plt) =100x109/L Biochemistry: • Serum total bilirubin = 1.5 x ULN • Serum albumin > 2.5 g/dl • Serum creatinine = 1.5 x ULN or 24-hour clearance = 50 ml/min. • AST/SGOT and ALT/SGPT = 2.5 x Upper Limit of Normal (ULN) or = 5.0 x ULN if liver metastases are present
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 26
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

1.Evidence of spinal cord compression or current evidence of CNS metastases. CT/MRI of the brain is mandatory (within 3 weeks before study start) in case of clinical suspicion or evidence of brain metastases 2.Patients who are < 4 weeks since last chemotherapy or treatment with another systemic anti-cancer agent. Patients must have recovered (CTC = 1) from acute toxicities of any previous therapy (with the exception of alopecia). 3. Patients may have received prior radiotherapy for management of local disease providing that disease progression has been documented, all toxicities have resolved (CTC = 1) (with the exception of alopecia), and the last fraction of radiotherapy was completed at east 4 weeks prior to the study. 4.Prior treatment with an agent that acts via HER2/c-erbB2 targeting other than 1st line trastuzumab, include (but are not limited to) lapatinib and pertuzumab. 5.Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted) 6. Patients with malignant ascites that require invasive treatment 7.Patients with acute or chronic renal disease; and active and chronic liver disease requiring intervention. Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol. 8.Major surgery = 2 weeks prior to enrollment or who have not recovered from such therapy 9.Impaired cardiac function, including any one of the following: a. History (or family history) of long QT syndrome b. Mean QTc = 450 msec on baseline ECG ?c. History of clinically manifested ischemic heart disease = 6 months prior to study start d. History of heart failure or left ventricular (LV) dysfunction (LVEF = 50%) by MUGA or ECHO e. Clinically significant ECG abnormalities f.History or presence of atrial fibrillation, atrial flutter or ventricular arrhythmias including ventricular tachycardia or Torsades de Pointes g. 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) h. Clinically significant resting bradycardia (< 50 beats per minute) i. 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. j. Obligate use of a cardiac pacemaker 10.Concurrent malignancies or invasive cancers diagnosed within the past 5 years, except for adequately treated basal cell cancer of the skin or in situ cancer of the cervix 11.Patients receiving chronic or high dose corticosteroids therapy (Inhaled steroids and short courses of oral steroids for anti-emesis or as an appetite stimulant are allowed) 12. Patients unwilling or unable to comply with the protocol 13.Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggesting HIV infection. 14.Known hypersensitivity to any of the study drugs or their excipients. See protocol for the remaining crriteria (15-17)

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 preliminary efficacy of AUY922 in combination with trastuzumab standard therapy, using Objective Response Rate (ORR), as per investigator, in advanced HER2+ gastric cancer patients progressing on 1st line trastuzumab containing treatment;Secondary Objective: - To estimate Progression Free Survival (PFS) - To estimate Overall Survival (OS) - To estimate Disease Control Rate (DCR) - To evaluate the safety and tolerability of AUY922 when administered in combination with trastuzumab standard therapy - To characterize the pharmacokinetic profile of AUY922 when given in combination with trastuzumab standard therapy;Primary end point(s): Overall Response Rate (ORR) per RECIST;Timepoint(s) of evaluation of this end point: every six weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): - Progression free survival (PFS) per RECIST - Overall Survival - Disease Contraol Rate (DCR) as per RECIST - Adverse drug reactions, changes in hematology and chemistry values, specifically those associated with hepatic and renal function; assessment of physical examinations, ocular examinations, neurological exams, and electrocardiograms - Exposure of AUY922 in plasma;Timepoint(s) of evaluation of this end point: at the protocol defined timepoints (PFS, DCR, PK) or throughout the tratment period (safety, survival)

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