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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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EUCTR |
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Last refreshed on:
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30 June 2019 |
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Main ID: |
EUCTR2007-002449-19-FR |
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Date of registration:
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19/11/2007 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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A phase Ib/IIa, trial of LBH589 in combination with trastuzumab in adult female patients with HER2 positive metastatic breast cancer whose disease has progressed during or following therapy with trastuzumab
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Scientific title:
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A phase Ib/IIa, trial of LBH589 in combination with trastuzumab in adult female patients with HER2 positive metastatic breast cancer whose disease has progressed during or following therapy with trastuzumab |
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Date of first enrolment:
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18/02/2008 |
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Target sample size:
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118 |
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Recruitment status: |
Not Recruiting |
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URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002449-19 |
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Study type:
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Interventional clinical trial of medicinal product |
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Study design:
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Controlled: no
Randomised:
Open:
Single blind:
Double blind:
Parallel group:
Cross over:
Other:
If controlled, specify comparator, Other Medicinial Product:
Placebo:
Other:
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Phase:
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Human pharmacology (Phase I): yes
Therapeutic exploratory (Phase II): yes
Therapeutic confirmatory - (Phase III): no
Therapeutic use (Phase IV): no
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Countries of recruitment
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France
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Germany
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Italy
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United Kingdom
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Contacts
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Key inclusion & exclusion criteria
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Inclusion criteria:
• 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
• Serum potassium > LLN
• Serum sodium = LLN
• Serum albumin = LLN or 3g/dl
• Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
• TSH and free T4 within normal limits (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
Exclusion criteria:
• 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 LBH589
• 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)
• 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
• Concomitant use of CYP3A4/5 inhibitors
• Active bleeding diathesis or on any treatment with therapeutic doses of sodium warfarin or any other anti-vitamin K drug (INR value above 1.5). Low doses of sodium warfarin (e.g., = 2 mg/day), or low doses of any other anti-vitamin K drug, for line patency is allowable
• 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
Age minimum:
Age maximum:
Gender:
Female: yes
Male: no
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Health Condition(s) or Problem(s) studied
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HER positive metastatic breast cancer
MedDRA version: 9.1
Level: LLT
Classification code 10027475
Term: Metastatic breast cancer
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Intervention(s)
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Product Code: LBH589C
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: panobinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Product Code: LBH589C
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: panobinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589C
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Product Code: LBH589C
Pharmaceutical Form: Solution for injection
INN or Proposed INN: parabinostat
CAS Number: 404950-80-7
Current Sponsor code: LBH589C
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Trade Name: Herceptin
Product Name: Herceptin
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: trastuzumab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 21-
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Primary Outcome(s)
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Primary end point(s): Primary endpoints: DLT during dose escalation, overall anti-tumor response rate at the MTDs during dose expansion
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Main Objective: • During dose escalation, to determine the MTD of LBH589 that can be combined with trastuzumab, in patients with HER2-positive MBC whose disease has progressed on or after trastuzumab:
Arm 1 - Determine the MTD of LBH589 i.v. given on D1, D8 as part of a 21 day cycle, combined with standard doses of trastuzumab in patients with HER2-positive MBC
Arm 2 - Determine the MTD of oral LBH589 given twice weekly (e.g. Monday/Thursday) for two consecutive weeks as part of a 21 day cycle, combined with standard doses of trastuzumab in patients with HER2-positive MBC
• During expansion of the MTD, to preliminarily explore the anti-tumor activity of i.v. and oral LBH at their respective MTDs when combined with trastuzumab using RECIST criteria
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Secondary Objective: • To evaluate the safety and tolerability profile of i.v. / oral LBH589 when given in combination with trastuzumab
• To evaluate the preliminary efficacy of i.v. / oral LBH589 when given in combination with trastuzumab using RECIST criteria
• To characterize the PK profile of i.v. and oral LBH589 after single and multiple doses when given in combination with trastuzumab (dose escalation only)
• To monitor the QTc interval in patients receiving i.v. and oral LBH589 when combined with trastuzumab
• To characterize potential biological factors, such as serum HER2 ECD, circulating tumor cells and apoptosis markers, that could correlate with efficacy and response (additional exploratory and/or optional biomarkers may be evaluated.) See Biomarker section
• At the end of dose expansion phase, a risk-benefit analysis will be performed in the population evaluable for efficacy, to assess both risk (safety) and benefit (efficacy) for both the oral and iv arms of LBH589
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Secondary ID(s)
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CLBH589C2204
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2007-002449-19-IT
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Source(s) of Monetary Support
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Ethics review
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Status: Approved
Approval date:
Contact:
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