Breast CancerPhase 2NCT00777049
Study of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer
A Phase 2 study testing Panobinostat in people with Breast Cancer, run by Translational Research in Oncology at 1 site in United States.
Trial summary
The purpose of the study is to assess the benefit of oral panobinostat monotherapy given to women with HER2-negative locally recurrent or 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
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Apr 2015
- Phase
- Phase 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
- Written informed consent obtained prior to any study-related procedures
- Women ≥ 18 years old
- Patients with an ECOG performance status of ≤ 2 assessed within 2 weeks (14 days) prior to registration
- Histologically or cytologically confirmed breast cancer with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- Measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines
- HER2-negative patients by local laboratory testing (IHC 0 or 1+ staining, IHC 2+ staining but in situ hybridization negative, or in situ hybridization negative).
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- ER and PgR testing from a local laboratory is required prior to patient registration
- For Arm I: at least two lines of prior endocrine therapy (in adjuvant and/or metastatic settings) are required. Up to two prior cytotoxic chemotherapies are allowed in the metastatic setting (prior adjuvant and neoadjuvant chemotherapy is allowed).
- For Arm II: up to 2 prior cytotoxic chemotherapy regimens for treatment of metastatic or locally recurrent breast cancer are allowed.
- Complete radiological tumor measurement within 4 weeks (28 days) prior to registration:
- Chest: CT scan with intravenous contrast if the contrast is not medically contraindicated or MRI
- Abdomen: CT scan with intravenous or oral contrast if the contrast is not medically contraindicated or MRI
- Brain: CT scan or MRI
- Bone: Whole body Bone Scintigraphy
- Patients must meet the following laboratory criteria within 2 weeks (14 days) prior to registration:
- Hematology
- Neutrophil count of > 1200/mm3
- Platelet count of > 100,000/mm3
- Hemoglobin ≥ 90 g/L
- Biochemistry
- AST/SGOT and ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to disease involvement
- Serum bilirubin ≤ 1.5 x ULN
- Serum creatinine ≤ 1.5 x ULN or 24-hour creatinine clearance ≥ 50 mL/min
- Serum potassium, sodium, magnesium, phosphorus, and calcium within normal limits for the institution
- Serum albumin ≥ LLN or 30g/L
- Clinically euthyroid function (TSH and free T4). (Patients are permitted to receive thyroid hormone supplements to treat underlying hypothyroidism).
- LVEF assessment (2-D echocardiogram or MUGA scan) performed within 6 weeks prior to registration, showing a LVEF value > 50%
- Electrocardiogram performed within 1 week prior to registration (details about findings on the Electrocardiogram that are not acceptable for participating in the study are reported in the Exclusion criteria section)
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days prior to registration and agree to appropriate method of pregnancy prevention.
- Patient should have an archival tumor sample available for confirmation of HER2, Estrogen and Progesterone status by the central lab.
Who cannot join
- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- Patients who need valproic acid for any other medical condition during the study or within 5 days prior to first panobinostat treatment
- Patients who have received prior systemic anti-cancer therapy (cytotoxic chemotherapy, endocrine therapy, targeted therapy, monoclonal antibody or biologic therapy) or investigational agent within the last 4 weeks prior to registration (6 weeks for nitrosoureas and mitomycin; 2 weeks for capecitabine)
- Patients who have received prior radiotherapy to ≥ 25% of the bone marrow within the last 4 weeks prior to registration; local radiotherapy is allowed however all recently irradiated lesions should not be included in the measurable disease assessment.
- Patients who have received prior investigational agents within the last 4 weeks prior to registration
- Patients with unresolved diarrhea ≥CTCAE grade 1
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- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat
- History of cardiac dysfunction including any one of the following:
- Complete left bundle branch block or obligate use of a cardiac pacemaker or congenital long QT syndrome or history or presence of ventricular tachyarrhythmias or clinically significant resting bradycardia (<50 beats per minute) or QTcF > 450 msec on screening ECG or right bundle branch block and left anterior hemiblock (bifascicular block)
- Presence of unstable atrial fibrillation (ventricular response rate >100 bpm). Patients with stable atrial fibrillation are allowed in the study provided they do not meet the other cardiac exclusion criteria
- Previous history angina pectoris or acute MI within 6 months of registration
- Congestive Heart Failure (New York Heart Association functional classification III-IV)
- History of unexplained syncope
- Other clinically significant heart disease (e.g. cardiomyopathy, cardiac artery disease, uncontrolled hypertension, or history of poor compliance with an antihypertensive regimen)
- Family history of long QT syndrome, unexplained syncope or unexplained sudden death
- Acute or chronic liver or renal disease
- Other concurrent severe and/or uncontrolled medical conditions (e.g., uncontrolled diabetes mellitus, active untreated or uncontrolled infection, chronic obstructive or chronic restrictive pulmonary disease including dyspnoea at rest from any cause) that could cause unacceptable safety risks or compromise compliance with the protocol
- Concomitant use of drugs with a risk of causing torsades de pointes where such treatments cannot be discontinued or switched to a different medication prior to starting study drug
- Brain metastases, unless patient randomized on study at least 90 days from completion of brain radiotherapy and / or surgery without radiologic or functional evidence of progressive brain metastases, and off corticosteroids above the dose of 7.5 mg prednisone or equivalent; No concurrent radiotherapy for brain metastasis is allowed
- Clinically significant third space fluid accumulation
- Concurrent biphosphonates unless if initiated prior to study entry (at least 4 weeks before patient registration)
- Pregnant (i.e., positive beta-human chorionic gonadotropin test) or breast feeding patient
- Unable to swallow oral medications
- Not willing to use a double barrier method of non-hormonal birth control. Contraception must be used during the study and for 30 days after last dose of study treatment.
- Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II, Open-label Multicenter Trial of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer
The purpose of the study is to assess the benefit of oral panobinostat monotherapy given to women with HER2-negative locally recurrent or metastatic breast cancer.
Read the detailed description
This was a phase II, open label, multi-centre, two-arm, two-stage design, international study of oral panobinostat in women with HER2-negative locally recurrent or metastatic breast cancer.
In the first stage of the trial, 21 evaluable patients HR+ (ER+ and/or PgR+), HER2-negative, were to be treated (Arm I); if less than 3 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective. In the other arm, 27 evaluable patients HR- (ER- and PgR-), HER2-negative, were to be treated (Arm II); if less than 2 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective.
Given these protocol conditions, the study was stopped in Arm II due to low recruitment as there was insufficient data available to draw conclusions regarding efficacy in that arm. It should also be noted that only one response was observed in this group.. In Arm I, among the 25 evaluable patients, the study did not achieve the required number of tumor responses to allow enrolment to continue.
As such the protocol was amended to stop enrolment and remove analysis of the initially planned secondary objectives (Progression Free Survival and Overall Survival) considering the small study sample size. The patients already included were given the option to continue in the study until they reached their planned end-of-study visit.
- Conditions
- Breast Cancer
- Being tested
- 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
Also called LBH589
Hard gelatine capsule - 5mg and 20mg
| Study group | Role | What they receive |
|---|---|---|
| ER+ and/or PgR+ (Arm I) | Experimental | Panobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle. Receives: Drug: Panobinostat |
| ER- and PgR- (Arm II) | Experimental | Panobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle. Receives: Drug: Panobinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR.
The assessment of overall response (OR) is based on the response of target lesion, of non-target lesion, and on presence of new lesions (RECIST criteria version 1.0 using imaging techniques; as per investigator assessment).
Measured: 6 years and 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2008 (estimated)
- Study startFeb 2009
- Primary completionApr 2015
- Study completionApr 2015
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.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Translational Research in Oncology
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sara Hurvitz, MD, Study chair, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00777049
- Sponsor's protocol ID
- TRIO 017
- Status last verified
- Jul 2016
- First submitted
- 21 Oct 2008
- Last updated
- 15 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Open-label Multicenter Trial of Panobinostat Monotherapy in Women With HER2-negative Locally Recurrent or Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00777049
- Acronym / sponsor ID
- TRIO 017
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Translational Research in OncologyUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 22 Oct 2008 (estimated)
- Results
- Posted 15 Jul 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the benefit of oral panobinostat monotherapy given to women with HER2-negative locally recurrent or metastatic breast cancer.
Detailed description
This was a phase II, open label, multi-centre, two-arm, two-stage design, international study of oral panobinostat in women with HER2-negative locally recurrent or metastatic breast cancer.
In the first stage of the trial, 21 evaluable patients HR+ (ER+ and/or PgR+), HER2-negative, were to be treated (Arm I); if less than 3 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective. In the other arm, 27 evaluable patients HR- (ER- and PgR-), HER2-negative, were to be treated (Arm II); if less than 2 responses were observed, that arm would be stopped and the treatment in this patient population would be declared as ineffective.
Given these protocol conditions, the study was stopped in Arm II due to low recruitment as there was insufficient data available to draw conclusions regarding efficacy in that arm. It should also be noted that only one response was observed in this group.. In Arm I, among the 25 evaluable patients, the study did not achieve the required number of tumor responses to allow enrolment to continue.
As such the protocol was amended to stop enrolment and remove analysis of the initially planned secondary objectives (Progression Free Survival and Overall Survival) considering the small study sample size. The patients already included were given the option to continue in the study until they reached their planned end-of-study visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ER+ and/or PgR+ (Arm I) | Experimental | Drug: PanobinostatPanobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle. |
| ER- and PgR- (Arm II) | Experimental | Drug: PanobinostatPanobinostat oral 40 mg (3 times a week) given every other week as part of a 28 day cycle. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (30 listed)
- Written informed consent obtained prior to any study-related procedures
- Women ≥ 18 years old
- Patients with an ECOG performance status of ≤ 2 assessed within 2 weeks (14 days) prior to registration
- Histologically or cytologically confirmed breast cancer with locally recurrent or radiological evidence of metastatic disease. Locally recurrent disease must not be amenable to resection with curative intent.
- Measurable disease per RECIST (Response Evaluation Criteria in Solid Tumor) guidelines
Key exclusion criteria (25 listed)
- Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
- Patients who need valproic acid for any other medical condition during the study or within 5 days prior to first panobinostat treatment
- Patients who have received prior systemic anti-cancer therapy (cytotoxic chemotherapy, endocrine therapy, targeted therapy, monoclonal antibody or biologic therapy) or investigational agent within the last 4 weeks prior to registration (6 weeks for nitrosoureas and mitomycin; 2 weeks for capecitabine)
- Patients who have received prior radiotherapy to ≥ 25% of the bone marrow within the last 4 weeks prior to registration; local radiotherapy is allowed however all recently irradiated lesions should not be included in the measurable disease assessment.
- Patients who have received prior investigational agents within the last 4 weeks prior to registration
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 |
|---|---|---|
| PanobinostatAlso: LBH589Hard gelatine capsule - 5mg and 20mg | Drug | ER+ and/or PgR+ (Arm I), ER- and PgR- (Arm II) |
Primary outcome
Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR.
Time frame: 6 years and 2 months
The assessment of overall response (OR) is based on the response of target lesion, of non-target lesion, and on presence of new lesions (RECIST criteria version 1.0 using imaging techniques; as per investigator assessment).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Sara Hurvitz, MD study chair
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Panobinostat in people with Breast Cancer, run by Translational Research in Oncology at 1 site in United States.
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 30 inclusion and 25 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: finished, as of the sponsor's last update on 15 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 phase mean?
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 15 Jul 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?
Objective Response Rate (as Determined by Investigator): the Percentage of Patients Assigned to a Treatment Arm With a Confirmed Best Response of CR or PR. (time frame: 6 years and 2 months). 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 15 Jul 2016.