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 - ND

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-002449-19-IT
• Date of registration: 17/10/2007
• Prospective Registration: Yes
• Primary sponsor: NOVARTIS FARMA
• Public title: 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 - ND
• Scientific title: 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 - ND
• Date of first enrolment: 08/05/2008
• Target sample size: 118
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-002449-19
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

France, Germany, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Inclusion 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 month of study entry Up to 2 prior chemotheraphy regimens for treatment of MBC (including chemotherapy treatment in combination with trastuzumab) Patients must meet the following laboratory criteria: pls see 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 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). pls see protocol


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

metastatic breast cancer
MedDRA version: 9.1 Level: LLT Classification code 10055113 Term: Breast cancer metastatic

Intervention(s)

Product Name: LBH589C
Product Code: LBH589C
Pharmaceutical Form: Capsule, hard
Current Sponsor code: panobinostat
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 25-

Product Name: LBH589C
Product Code: LBH589C
Pharmaceutical Form: Capsule, hard
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 5-

Trade Name: HERCEPTIN
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: Trastuzumab
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Product Name: LBH589C
Product Code: LBH589C
Pharmaceutical Form: Capsule, hard
Current Sponsor code: panobinostat
Concentration unit: mg/g milligram(s)/gram
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)

Main Objective: Primary: 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

Primary end point(s): Primary endpoints: DLT during dose escalation, overall anti-tumor response rate at the MTDs during dose expansion

Secondary Objective: Secondary: 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 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 pls see protocol

Secondary ID(s)

LBH589C2204