A phase Ib, open-label, two arm study of i.v. and oral panobinostat (LBH589) in combination with i.v. trastuzumab (Herceptin®) and i.v. paclitaxel as treatment for adult female patients with HER2 overexpressing metastatic breast cancer (MBC)
- Conditions
- 10027476HER2 overexpressing metastatic breast cancer (MBC) / Metastatic Breast Cancer (MBC)
- Registration Number
- NL-OMON32569
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 10
* 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 < LLIN, but must be documented as corrected prior to patients enrolling on the study
* Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first administration of study treatment and must be willing to use adequate methods of contraception during the study and for 3 months after last study drug administration
* 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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary endpoints:<br /><br>* Determination of maximum tolerated dose (MTD) of i.v. and oral panobinostat<br /><br>when given in combination with paclitaxel and trastuzumab</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary endpoints:<br /><br>* AEs as determined by CTCAE version 3 and SAEs<br /><br>* ECG parameters<br /><br>* Pharmacokinetic parameters (for paclitaxel and panobinostat)<br /><br>* Tumor assessment according to RECIST<br /><br><br /><br>Exploratory endpoints (at MTD during expansion phase):<br /><br>* HER2 ECD and apoptosis markers in serum; cellular and molecular markers in<br /><br>tumor</p><br>