A Trial l of Panobinostat Given in Combination With Trastuzumab and Paclitaxel in Adult Female Patients With HER2 Positive Metastatic Breast Cancer

Study Overview
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Brief Summary
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The primary purpose of this study is to identify the maximum tolerated dose (MTD) of both intravenous and oral panobinostat when given in combination with trastuzumab and paclitaxel. The study will evaluate safety and efficacy of the combination in adult female patients with HER2+ metastatic breast cancer

Official Title
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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
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HER-2 Positive Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
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* Drug: IV LBH589
* Drug: Oral LBH589
* Drug: trastuzumab
* Drug: paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 year old Confirmed HER2+ metastatic breast cancer Prior treatment and progression on trastuzumab Patients must have adequate organ functions Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 Exclusion Criteria: Patients who have had surgery within last 2 weeks prior to starting the treatment Patients who receive concurrent therapy for brain metastases Impaired heart function or clinically significant heart disease Ongoing diarrhea Liver or renal disease with impaired hepatic or renal functions Concomitant use of any anti-cancer therapy or certain drugs Female patients who are pregnant or breast feeding Patients not willing to use an effective method of birth control Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IV LBH589 + trastuzumab + paclitaxel<br>i.v. panobinostat | Drug: IV LBH589<br> <br> Drug: trastuzumab<br> <br> Drug: paclitaxel<br> <br> |
| Experimental: Oral LBH589 + trastuzumab + paclitaxel<br>oral panobinostat | Drug: IV LBH589<br> <br> Drug: Oral LBH589<br> <br> Drug: trastuzumab<br> <br> Drug: paclitaxel<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the maximum tolerated dose of oral panobinostat in combination with trastuzumab and paclitaxel. Determine the maximum tolerated dose of iv LBH in combination with trastuzumab and paclitaxel. |  | At least 21 day cycle for both arms | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability throughout the study for both IV and oral arms to determine the recommended dose for phase ll trials. |  | 4 weeks after end of treatment | 
| To evaluate the efficacy in the expansion phase of the trial when the MTD is defined. |  | throughout the study and 4 weeks after end of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LBH589, Breast Cancer, HER2 positive, adult-female, HDAC inhibitor, panobinostat, metastatic breast, adult female patients