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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

This study has been terminated.
(The study was terminated early due to insufficient evidence of clinical benefit.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00567879
First received: December 4, 2007
Last updated: April 4, 2016
Last verified: March 2016
  Purpose
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 Intervention Phase
Breast Cancer
Drug: Panobinostat
Drug: Trastuzumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicities (DLTs) [ Time Frame: day 21 ] [ Designated as safety issue: Yes ]
    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:
  • Number of Participants With Best Overall Response [ Time Frame: day 21 ] [ Designated as safety issue: No ]
    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.


Enrollment: 56
Study Start Date: April 2008
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00567879

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:
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00567879     History of Changes
Other Study ID Numbers: CLBH589C2204  2007-002449-19 
Study First Received: December 4, 2007
Results First Received: April 4, 2016
Last Updated: April 4, 2016
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ministry of Health
Canada: Health Canada
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Breast Cancer
HER2 positive
adult-female
LBH589
HDAC inhibitor
panobinostat

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Panobinostat
Trastuzumab
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016