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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

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Panobinostat
Trastuzumab
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring Breast Cancer, HER2 positive, adult-female, LBH589, HDAC inhibitor, panobinostat

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • University of California at Los Angeles
  • University of Colorado Dept. of Univ. of Colorado
  • Norwalk Hospital Dept of Norwalk Hospital (2)
  • VA Maryland Health Care Dept.of GreenbaumCancerCent(3)
  • The Center for Cancer Care and Research
  • Ohio State Comprehensive Cancer Center/James Cancer Hospital SC
  • University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site
  • Novartis Investigative Site

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Panobinostat with trastuzumab

Arm Description

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

Outcomes

Primary Outcome Measures

Number of Participants With Dose Limiting Toxicities (DLTs)
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
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.

Full Information

First Posted
December 4, 2007
Last Updated
April 4, 2016
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00567879
Brief Title
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
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 Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early due to insufficient evidence of clinical benefit.
Study Start Date
April 2008 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. 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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
Breast Cancer, HER2 positive, adult-female, LBH589, HDAC inhibitor, panobinostat

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Panobinostat with trastuzumab
Arm Type
Experimental
Arm Description
Panobinostat intravenously (i.v.) or orally was given in combination with trastuzumab.
Intervention Type
Drug
Intervention Name(s)
Panobinostat
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Intervention Description
Fixed doses of trastuzumab were given in parallel with panobinostat. Trastuzumab i.v. was given weekly according to the instruction in the package insert.
Primary Outcome Measure Information:
Title
Number of Participants With Dose Limiting Toxicities (DLTs)
Description
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.
Time Frame
day 21
Secondary Outcome Measure Information:
Title
Number of Participants With Best Overall Response
Description
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.
Time Frame
day 21

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
University of California at Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
University of Colorado Dept. of Univ. of Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Norwalk Hospital Dept of Norwalk Hospital (2)
City
Norwalk
State/Province
Connecticut
ZIP/Postal Code
06856
Country
United States
Facility Name
VA Maryland Health Care Dept.of GreenbaumCancerCent(3)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
The Center for Cancer Care and Research
City
St. Louis
State/Province
Missouri
ZIP/Postal Code
63141
Country
United States
Facility Name
Ohio State Comprehensive Cancer Center/James Cancer Hospital SC
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Facility Name
Novartis Investigative Site
City
Kelowna
State/Province
British Columbia
ZIP/Postal Code
V1Y 5L3
Country
Canada
Facility Name
Novartis Investigative Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Novartis Investigative Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
Facility Name
Novartis Investigative Site
City
Dijon Cedex
ZIP/Postal Code
21034
Country
France
Facility Name
Novartis Investigative Site
City
Paris
ZIP/Postal Code
75231
Country
France
Facility Name
Novartis Investigative Site
City
Saint-Herblain Cédex
ZIP/Postal Code
44805
Country
France
Facility Name
Novartis Investigative Site
City
Heidelberg
ZIP/Postal Code
69115
Country
Germany
Facility Name
Novartis Investigative Site
City
Meldola
State/Province
FC
ZIP/Postal Code
47014
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
State/Province
GE
ZIP/Postal Code
16132
Country
Italy
Facility Name
Novartis Investigative Site
City
Modena
State/Province
MO
ZIP/Postal Code
41100
Country
Italy
Facility Name
Novartis Investigative Site
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
London
ZIP/Postal Code
W12 0HS
Country
United Kingdom
Facility Name
Novartis Investigative Site
City
Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://www.novartisclinicaltrials.com/etrials/searchTrial.do?trialID=674
Description
Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.
URL
http://www.breastcancerresearchstudy.com
Description
Breast Cancer

Learn more about this trial

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

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