locally advanced or metastatic HER2-positive breast cancer, that has progressed after or during at least one Trastuzumab-containing regimen MedDRA version: 13.1 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 13.1 Level: PT Classification code 10055113 Term: Breast cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Female pts with confirmed HER2-positive, non-operable locally advanced or metastatic breast cancer. Tumor samples of HER2-positive patients must demonstrate HER2 over-expression based on either: Immunohistochemistry (IHC) at the 3+ level, or IHC 2+ confirmed by fluorescence in-situ hybridization (FISH). Tumors tested by FISH must be positive by the specific FISH assay for the amplification of HER2. • Patients must have received at least 1 but no more than 2 prior anti-HER2 based regimens including at least 1 regimen containing Trastuzumab. If recurrence occurred during adjuvant therapy, or = 12 months after completion of adjuvant Trastuzumab-containing therapy, the patient is eligible. In this case the adjuvant therapy will be considered as one line of treatment for advanced disease. • Patients must have at least one measurable lesion as defined by RECIST. Irradiated lesions are only evaluable for disease progression. • All patients must have documented progressive disease following the last line of therapy before entering the study. • Patients who fulfill 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 with a tumor-background ratio = 2 - able to lie still and flat on the table • Age = 18 years • ECOG Performance Status of = 1 • Able to sign informed consent and to comply with the protocol • Patients must have laboratory values as specified in the protocol 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
Exclusion criteria: • Patients with known 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 • Prior treatment with any HSP90 or HDAC inhibitor. • Patients who received systemic anti-cancer treatment prior to the first dose of AUY922 within the following time frames: - Radiotherapy, conventional chemotherapy, hormonotherapy, investigational drugs and monoclonal antibodies other than Trastuzumab: within 4 weeks - Palliative radiotherapy: within 2 weeks - Nitrosoureas, mitomycin: within 6 weeks • Patients with unresolved diarrhea = CTCAE grade 1 • Patients who have not recovered from the reversible side effects of previous systemic anticancer therapy (except for alopecia) to less than CTCAE grade 2 prior to the first dose. • Treatment with therapeutic doses of sodium warfarin (Coumadin). Low doses of Coumadin (e.g. < 2mg/day for line patency) are permitted. • Pregnant or lactating women. • Fertile women of childbearing potential (WCBP) not using adequate contraception (abstinence, oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile). • Patients with acute or chronic liver or renal disease. • Patients with other concurrent severe and/or uncontrolled medical conditions (e.g. uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol. • Known hypersensitivity to any study medication. • Impaired cardiac function • Patients unwilling or unable to comply with the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary objective of phase Ib: Define the maximum tolerated dose (MTD) and/or the recommended phase two dose (RPTD) of AUY922 in combination with Trastuzumab when administered I.V. on a once weekly schedule to adult patients with advanced or metastatic HER2-positive breast cancers. Primary objective of phase II: Evaluate preliminary anti-tumor activity of AUY922 in combination with trastuzumab in adult patients with advanced or metastatic HER2- positive breast cancers. ;Secondary Objective: Secondary objectives of phase Ib: •Characterize the safety and tolerability of AUY922 when administered in combination with Trastuzumab. •Characterize the pharmacokinetic profile of AUY922 and its metabolite BJP762, when given in combination with Trastuzumab. Secondary objectives of phase II: •Characterize the safety and tolerability of the combination at the RPTD •Assess the efficacy at the RPTD (e.g. Progression Free Survival (PFS), Overall Survival (OS)) •Characterize the pharmacokinetic profile of AUY922 and its metabolite BJP762, when given in combination with Trastuzumab •Evaluate the pharmacodynamic effect of AUY922 and Trastuzumab on HSP90 client proteins in blood and tumor tissue ;Primary end point(s): Primary endpoint of phase Ib: • Incidence rate of Dose-Limiting Toxicities (DLT) Primary endpoint of phase II: •Overall response rate (ORR) Secondary endpoints of phase II: • Safety: Adverse drug reactions and serious adverse drug reactions, changes in hematology and chemistry values, specifically those associated with hepatic and renal function; and assessment of physical examinations, neurological exams, vital signs and electrocardiograms. •PFS/OS as defined in RECIST guidelines • Pharmacokinetics: Exposure of AUY922 in plasma. PK parameters such as AUC, Cmax, Ctrough and t1/2 • Temporal and magnitude changes in blood and tissue of relevant biomarkers levels comparing pre- vs. post-treatment | — |
Countries
France, Germany, Netherlands, Sweden, United Kingdom
Contacts
Public ContactMedicinsk information
Novartis Sverige AB
Outcome results
None listed