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: LLTClassification code 10066896Term: HER-2 positive gastric cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); 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-DE
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-09-20
• Last Update Posted: 3 February 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Patients eligible for inclusion in this study have to meet all of the following criteria:
- Written informed consent obtained prior to any screening procedures
- Patients with documented cytological or histological confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma and proven HER2 positive.
- Patients with progressive disease (radiological confirmation required according to RECIST) after first line of trastuzumab in combination with chemotherapy for advanced gastric cancer.
- Age = 18 years or age of consent in country of residence and able to sign Informed Consent
- ECOG performance status of 0-1 at study entry
- HER2-overexpressing positive gastric tumor by IHC3+ or IHC2+ with positive in situ hybridization
- Measurable disease according to RECIST (Irradiated lesions can not be considered measurable unless they have clearly progressed since radiotherapy).
- 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.
- Patients must have hematologic and biochemistry laboratory values as defined in the protocol

Other inclusion criteria may apply.
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

Patients eligible for this study must not meet any of the following criteria:
- 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
- Patient must be = 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).
- 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 least 4 weeks prior to the study.
- 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.
- Treatment with therapeutic doses of coumarin-type anticoagulants. (Maximum daily dose of 2 mg, for line patency permitted)
- Patients with malignant ascites that require invasive treatment
- 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.
- Major surgery = 2 weeks prior to enrollment or who have not recovered from such therapy
- Impaired cardiac function
- 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
- 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)
- Patients unwilling or unable to comply with the protocol
- Patients known to be HIV positive. Testing is not required in the absence of clinical signs and symptoms suggesting HIV infection.
- Known hypersensitivity to any of the study drugs or their excipients
- Participation in another clinical study within 30 days before first study treatment
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG laboratory test (> 5 mIU/mL).
- Fertile women of childbearing potential (WOCBP) not using adequate contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile).

Other exclusion criteria may apply.

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)<br>- To estimate Overall Survival (OS)<br>- To estimate Disease Control Rate (DCR)<br>- To evaluate the safety and tolerability of AUY922 when administered in combination with trastuzumab standard therapy<br>- To characterize the pharmacokinetic profile of AUY922 when given in combination with trastuzumab standard therapy<br>;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<br>- Overall Survival<br>- Disease Contraol Rate (DCR) as per RECIST<br>- 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<br>- Exposure of AUY922 in plasma ;Timepoint(s) of evaluation of this end point: at the protocol defined timepoints (PFS, DCR, PK) or throughout th etratment period (safety, survival)