HER2 overexpressing metastatic breast cancer (MBC) / Metastatic Breast Cancer (MBC)
Conditions
Interventions
If a patient participates in this study, he/shewill be asked to sign the
informed consent before any tests are performed specifically for this study.
After the patient sign the informed consent but
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: * Histologically or cytologically confirmed HER2 positive breast cancer * Female patients * 18 years old * ECOG performance status of * 1 * Non-measurable or measurable disease (according to RECIST) * Prior treatment for brain metastases is allowed but patient must be neurologically stable and off corticosteroids and not receiving concurrent radiotherapy for brain metastases * Prior treatment with trastuzumab and/or lapatinib is permitted. * If patient has received prior treatment with anthracylines, this must be completed * 24 weeks before the start of study treatment * Patient must have received at least one prior treatment regimen containing a taxane and up to 2 prior regimens for metastatic disease * Concurrent bisphosphonates are permitted if initiated prior to study entry * Patients must meet the specified values in the protocol concerning to haematology parameters and biochemistry parameters * Patients with elevated alkaline phosphatase due to bone metastasis can be enrolled * Patient who are clinically euthyroid (patients may be on thyroid hormone replacement) * Potassium, calcium, and magnesium supplements may be given to correct values that are
Exclusion criteria
Exclusion criteria: * Prior HDAC, DAC, HSP90 inhibitors or valproic acid administered for the treatment ofcancer * Need for valproic acid during the study or within 5 days prior to first panobinostat treatment * History of hypersensitivity reaction to paclitaxel or other drugs formulated with polysorbate 80 (Tween 80), polyethoxylated castor oil * Known allergy or severe reactions to paclitaxel and/or trastuzumab or its constituents * Prior chemotherapy within the last 3 weeks (exceptions: * 6 weeks for nitrosoureas or mitomycin, * 2 weeks for capecitabine or oral cyclophosphamide) before the start of study treatment * Prior treatment with investigational agents within the last 4 weeks before the start of study treatment * Surgery or not recovering within the last 2 weeks prior to starting study treatment * Presence of persistent * grade 2 neuropathy or history of grade 3/4 neuropathy * Presence of unresolved diarrhea *CTCAE grade 1 * Impaired cardiac function (see more details in the protocol) * Concomitant use of drugs with a risk of causing torsades de pointes where such treatment cannot be discontinued or switched to a different medication prior to starting study drug * Other concurrent severe and/or uncontrolled medical conditions that could cause unacceptable safety risks or compromise compliance with the protocol * Known history of HIV seropositivity * Active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin or any other anti-vitamin K drugs * Requirement of diuretics or draining procedures to manage or drain third space fluid accumulation * Bone marrow support, stem cell support at study entry * Pregnant or breast-feeding * History of non-compliance with medical treatments or with inability to grant a reliable written informed consent
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary endpoints: * Determination of maximum tolerated dose (MTD) of i.v. and oral panobinostat when given in combination with paclitaxel and trastuzumab | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary endpoints: * AEs as determined by CTCAE version 3 and SAEs * ECG parameters * Pharmacokinetic parameters (for paclitaxel and panobinostat) * Tumor assessment according to RECIST Exploratory endpoints (at MTD during expansion phase): * HER2 ECD and apoptosis markers in serum; cellular and molecular markers in tumor | — |
Countries
Netherlands
Outcome results
None listed