A Trial of Panobinostat and Trastuzumab for Adult Female Patients With HER2 Positive Metastatic Breast Cancer (MBC) Whose Disease Has Progressed on or After Trastuzumab

• ClinicalTrials.gov Identifier: NCT00567879
• Recruitment Status: Terminated
• First Posted: December 5, 2007
• Results First Posted: May 9, 2016
• Last Update Posted: May 9, 2016
• Sponsor: Novartis Pharmaceuticals
• Information provided by (Responsible Party): Novartis ( Novartis Pharmaceuticals )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Panobinostat; Drug: Trastuzumab	Phase 1; Phase 2

Detailed Description:

This phase Ib/IIa study was prematurely terminated due to lack of efficacy noted in 55 patients with HER2-positive MBC who had progressed on or following a trastuzumab-based therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 56 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2008
• Actual Primary Completion Date: May 2011
• Actual Study Completion Date: May 2011

Arms and Interventions

Arm

Intervention/treatment

Experimental: Panobinostat with trastuzumab; Panobinostat intravenously (i.v.) or orally was given in combination with trastuzumab.

Drug: Panobinostat; Participants received escalating doses of panobinostat until the maximum tolerated dose (MTD) was reached. The starting dose of panobinostat i.v. was 10mg/m^2 at days 1 and 8 during a 21-day treatment cycle. The oral panobinostat starting dose was 20 mg twice weekly.; Drug: Trastuzumab; Fixed doses of trastuzumab were given in parallel with panobinostat. Trastuzumab i.v. was given weekly according to the instruction in the package insert.; Other Name: Herceptin

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: day 21 ]
   Safety data was reviewed to determine the DLTs. DLTs comprised adverse events (AEs) or abnormal laboratory values that occurred at any time and were assessed as clinically relevant and meeting any of the following criteria: considered to be related to the study treatment and unrelated to disease, disease progression, inter-current illness, or concomitant medications. Toxicities were assessed using the National Cancer Institute common terminology criteria for adverse events (NCI CTCAE), version 3.0. Disease related symptoms were not considered a DLT.

Secondary Outcome Measures :

1. Number of Participants With Best Overall Response [ Time Frame: day 21 ]
   Tumors were assessed according to Response Evaluation Criteria in Solid tumors (RECIST). Complete response (CR): disappearance of all lesions (i.e. all evidence of disease, not just the target lesions) determined by 2 observations not less than 4 weeks apart; Partial response (PR): > 30% decrease in the sum of longest diameters of target lesions compared to baseline, with response or stable disease observed in non-target lesions, and no new lesions; Stable disease (SD): neither sufficient shrinkage to qualify for response or sufficient increase to qualify for progressive disease in target lesions, with response or stable disease observed in non-target lesions, and no new lesions; Progressive disease (PD): > 20% increase in the sum of longest diameters of target lesions compared to smallest sum longest diameter recorded. In addition, the sum must also demonstrate an absolute increase of at least 5mm.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion criteria:

• Age > 18 year old
• Confirmed HER2+ ve metastatic breast cancer
• Prior treatment and progression on trastuzumab
• Patients must have adequate laboratory values
• Eastern Cooperative Oncology Group (ECOG) performance status of <2

Key Exclusion criteria:

• Patients with active central nervous system (CNS) disease or brain metastases except those who have been previously treated and have been stable for at least 3 months.
• Impaired heart function or clinically significant heart disease
• Impairment of gastrointestinal (GI) function, or GI disease that may significantly alter the absorption of LBH589
• 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

Contacts and Locations

Locations

United States, California

University of California at Los Angeles

Los Angeles, California, United States, 90095

United States, Colorado

University of Colorado Dept. of Univ. of Colorado

Aurora, Colorado, United States, 80045

United States, Connecticut

Norwalk Hospital Dept of Norwalk Hospital (2)

Norwalk, Connecticut, United States, 06856

United States, Maryland

VA Maryland Health Care Dept.of GreenbaumCancerCent(3)

Baltimore, Maryland, United States, 21201

United States, Missouri

The Center for Cancer Care and Research

St. Louis, Missouri, United States, 63141

United States, Ohio

Ohio State Comprehensive Cancer Center/James Cancer Hospital SC

Columbus, Ohio, United States, 43210

United States, Pennsylvania

University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital

Pittsburgh, Pennsylvania, United States, 15232

Canada, British Columbia

Novartis Investigative Site

Kelowna, British Columbia, Canada, V1Y 5L3

Canada, Ontario

Novartis Investigative Site

Toronto, Ontario, Canada, M5G 2M9

Canada, Quebec

Novartis Investigative Site

Montreal, Quebec, Canada, H3T 1E2

France

Novartis Investigative Site

Dijon Cedex, France, 21034

Novartis Investigative Site

Paris, France, 75231

Novartis Investigative Site

Saint-Herblain Cédex, France, 44805

Germany

Novartis Investigative Site

Heidelberg, Germany, 69115

Italy

Novartis Investigative Site

Meldola, FC, Italy, 47014

Novartis Investigative Site

Genova, GE, Italy, 16132

Novartis Investigative Site

Modena, MO, Italy, 41100

United Kingdom

Novartis Investigative Site

Birmingham, United Kingdom, B15 2TH

Novartis Investigative Site

London, United Kingdom, W12 0HS

Novartis Investigative Site

Manchester, United Kingdom, M20 4BX

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals; Novartis Pharmaceuticals

More Information

Additional Information:

Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers. 

Breast Cancer 

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00567879
• Other Study ID Numbers: CLBH589C2204; 2007-002449-19 ( EudraCT Number )
• First Posted: December 5, 2007
• Results First Posted: May 9, 2016
• Last Update Posted: May 9, 2016
• Last Verified: March 2016

Keywords provided by Novartis ( Novartis Pharmaceuticals ):

Breast Cancer; HER2 positive; adult-female; LBH589; HDAC inhibitor; panobinostat

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Panobinostat; Antineoplastic Agents, Immunological; Antineoplastic Agents; Histone Deacetylase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action