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

December 4, 2007
April 4, 2016
April 2008
May 2011   (final data collection date for primary outcome measure)
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.
Determine the dose of oral LBH plus trastuzumab combination Determine the dose of iv LBH plus trastuzumab combination Explore preliminary anti-tumor activity of the combination
Complete list of historical versions of study NCT00567879 on ClinicalTrials.gov Archive Site
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.
Efficacy throughout the study Safety and tolerability throughout the study Explore potential biomarkers
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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
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
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
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.
Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Breast Cancer
  • 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
Experimental: Panobinostat with trastuzumab
Panobinostat intravenously (i.v.) or orally was given in combination with trastuzumab.
Interventions:
  • Drug: Panobinostat
  • Drug: Trastuzumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
56
May 2011
May 2011   (final data collection date for primary outcome measure)

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
Female
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada,   France,   Germany,   Italy,   United Kingdom
 
NCT00567879
CLBH589C2204, 2007-002449-19
Not Provided
Not Provided
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Novartis Pharmaceuticals
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP