A phase Ib/IIa, trial of panobinostat in combination with trastuzumab in adult female patients with HER2 positive metastatic breast cancer whose disease has progressed during or following therapy with trastuzumab
- Conditions
- HER positive metastatic breast cancer
- Registration Number
- EUCTR2007-002449-19-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 118
•Female patients = 18 years old
•Patients with an ECOG performance status of = 2
•Histologically or cytologically confirmed breast cancer with radiological evidence of metastatic disease.
•During dose escalation metastatic disease can be non-measurable or measurable.
•During recruitment of the additional patients for dose expansion, only measurable disease is acceptable
•History of HER2-positive MBC patients (ICH 3+ staining or FISH (+ve) or ICH 2+ only if FISH (+ve). Whenever it is feasible HER2 status should be confirmed at metastatic stage of the disease at baseline and post-treatment
•Prior trastuzumab-containing regimen (in neoadjuvant and/or adjuvant and/or metastatic setting) regardless of whether trastuzumab was given as monotherapy or in combination with chemotherapy. Any number of prior trastuzumab regimens is acceptable
• Radiological evidence of progression while on trastuzumab or within 6 months of last dose of trastuzumab
•Radiological evidence of progression on or following most recent therapy within three months of study entry
•Up to 2 prior chemotheraphy regimens for treatment of MBC (including chemotherapy treatment in combination with trastuzumab)
•Hormone receptor status: HR (ER/PR) positive or negative (or indeterminate)
•Patients must meet the following laboratory criteria:
•Hematology
•Neutrophil count of >1500/mm3
•Platelet count of > 100,000/mm3L
•Hemoglobin = 9 g/dL
•Biochemistry
•AST/SGOT and ALT/SGPT = 2.5 x upper limit of normal (ULN) or = 5.0 x ULN if the transaminase elevation is due to disease involvement
•Serum bilirubin = 1.5 x ULN
•Serum creatinine = 1.5 x ULN or 24-hour creatinine clearance = 50 ml/min
•Total serum calcium (corrected for serum albumin) or ionized calcium = LLN and =ULN
•Serum potassium > LLN and =ULN
•Serum sodium = LLN and =ULN
•Serum albumin = LLN or 3g/dl
•Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
•Clinically euthyroid (patients may be on thyroid hormone replacement)
•Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment and must be willing to use two methods of contraception, one of them being a barrier method, during the study and for 3 months after last study drug administration.
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
•Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
•Patients who need valproic acid for any other medical condition during the study or within 5 days prior to first LBH589 treatment
•Patients who have received prior chemotherapy within the last 4 weeks (6 weeks for nitrosoureas and mitomycin: 2 weeks for capecitabine)
•Patients who have received prior radiotherapy within the last 4 weeks
•Patients who have received prior investigational agents within the last 4 weeks
•Patients who have received prior radiotherapy to >30% of the bone marrow
•Patients with unresolved diarrhea > CTCAE grade 1
•Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
•Impaired cardiac function, including any one of the following:
•LVEF < 50% as determined by ECHO or MUGA
•Complete left bundle branch block or obligate use of a cardiac pacemaker or congenital long QT syndrome or history or presence of ventricular tachyarrhythmias or clinically significant resting bradycardia (<50 beats per minute) or QTc > 450 msec on screening ECG or right bundle branch block and left anterior hemiblock (bifasicular block)
•Medical history of long QTc syndrome
•Family history of sudden death
•Medical history of unexplained syncope
•Presence of unstable atrial fibrillation (ventricular response rate >100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
•Previous history angina pectoris or acute MI within 6 months
•New York Heart Association functional classification III-IV
•Other clinically significant heart disease (e.g. congestive heart failure, cardiomyopathy, cardiac artery disease, uncontrolled hypertension, or history of poor compliance with an antihypertensive regimen)
•Acute or chronic liver or renal disease
•Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes mellitus, active or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with 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
•Active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin or any other anti-vitamin K drugs
Note: mini-dose of Coumadin (e.g., 1 mg/day) or other agents given to maintain intravenous line patency, as well as unfractionated or low molecular weight heparin therapy is permitted.
•Uncontrolled or symptomatic brain metastasis (No concurrent radiotherapy for brain metastasis)
•Symptomatic pleural effusion
•Clinically significant third space fluid accumulation
•Concurrent biphosphonates allowed if initiated prior to study entry ( at least 4 weeks before study entry)
•Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method