Breast CancerPhase 1/2NCT00567879
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 1/2 study testing Panobinostat and Trastuzumab in people with Breast Cancer, run by Novartis Pharmaceuticals at 20 sites in 6 countries.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Panobinostat and Trastuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 20 sitesin 6 countries
- Study dates
- Apr 2008to May 2011
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
20 sites in 6 countries.
20 sites in 6 countries
United States7 sites
University of Colorado Dept. of Univ. of Colorado
Aurora, Colorado, 80045
VA Maryland Health Care Dept.of GreenbaumCancerCent(3)
Baltimore, Maryland, 21201
Ohio State Comprehensive Cancer Center/James Cancer Hospital SC
Columbus, Ohio, 43210
University of California at Los Angeles
Los Angeles, California, 90095
Norwalk Hospital Dept of Norwalk Hospital (2)
Norwalk, Connecticut, 06856
University of Pittsburgh Cancer Institute Dept of Magee Women's Hospital
Pittsburgh, Pennsylvania, 15232
The Center for Cancer Care and Research
St Louis, Missouri, 63141
Canada3 sites
Novartis Investigative Site
Kelowna, British Columbia, V1Y 5L3
Novartis Investigative Site
Montreal, Quebec, H3T 1E2
Novartis Investigative Site
Toronto, Ontario, M5G 2M9
France3 sites
Novartis Investigative Site
Dijon, 21034
Novartis Investigative Site
Paris, 75231
Novartis Investigative Site
Saint-Herblain Cédex, 44805
Italy3 sites
Novartis Investigative Site
Genova, GE, 16132
Novartis Investigative Site
Meldola, FC, 47014
Novartis Investigative Site
Modena, MO, 41100
United Kingdom3 sites
Novartis Investigative Site
Birmingham, B15 2TH
Novartis Investigative Site
London, W12 0HS
Novartis Investigative Site
Manchester, M20 4BX
About this study
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
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
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Panobinostat, Trastuzumab
- Keywords
- Breast Cancer, HER2 positive, adult-female, LBH589, HDAC inhibitor, panobinostat
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PanobinostatDrug
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.
TrastuzumabDrug
Also called Herceptin
Fixed doses of trastuzumab were given in parallel with panobinostat. Trastuzumab i.v. was given weekly according to the instruction in the package insert.
| Study group | Role | What they receive |
|---|---|---|
| Panobinostat with trastuzumab | Experimental | Panobinostat intravenously (i.v.) or orally was given in combination with trastuzumab. Receives: Drug: Panobinostat; Drug: Trastuzumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: day 21
Secondary outcomes (1)
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.
Measured: day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2007 (estimated)
- Study startApr 2008
- Primary completionMay 2011
- Study completionMay 2011
Why it stopped: The study was terminated early due to insufficient evidence of clinical benefit.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00567879
- Sponsor's protocol ID
- CLBH589C2204
- Other IDs
- 2007-002449-19
- Status last verified
- Mar 2016
- First submitted
- 4 Dec 2007
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00567879
- Acronym / sponsor ID
- CLBH589C2204
- Conditions
- Breast Cancer
- Keywords
- Breast Cancer, HER2 positive, adult-female, LBH589, HDAC inhibitor, panobinostat
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated early due to insufficient evidence of clinical benefit.
- Enrolment
- 56 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 5 Dec 2007 (estimated)
- Results
- Posted 9 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Panobinostat with trastuzumab | Experimental | Drug: Panobinostat, Drug: TrastuzumabPanobinostat intravenously (i.v.) or orally was given in combination with trastuzumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PanobinostatParticipants 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 | Panobinostat with trastuzumab |
| TrastuzumabAlso: HerceptinFixed doses of trastuzumab were given in parallel with panobinostat. Trastuzumab i.v. was given weekly according to the instruction in the package insert. | Drug | Panobinostat with trastuzumab |
Primary outcome
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.
1 secondary outcome
Number of Participants With Best Overall Response
Time frame: day 21
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
20 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Panobinostat and Trastuzumab in people with Breast Cancer, run by Novartis Pharmaceuticals at 20 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in United States, Canada, France, Italy, United Kingdom and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 May 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) (time frame: day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.