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Breast CancerEarly Phase 1NCT00993642

ERB-B4 After Treatment With HDAC Inhibitor in ER+ Tamoxifen Refractory Breast Cancer

A Early Phase 1 study testing Panobinostat (LBH589) in people with Breast Cancer, run by Tulane University Health Sciences Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The long-term objective of this research is to understand the molecular mechanisms of acquired endocrine resistance in breast cancer. Identifying these mechanisms is critical to the implementation of novel therapeutic strategies that can target and overcome altered gene networks involved in controlling 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 (LBH589)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Sep 2009to Dec 2010
Phase
Early Phase 1
Are there results?
None posted in the registry

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

  • Patient age is ≥ 18 years
  • Female
  • Stage IV tamoxifen-refractory breast cancer (progression of at least 25% in diameters of at least one measurable lesion while taking tamoxifen or occurrence of a new lesion while taking tamoxifen), including first occurrence of metastasis within 12 months of completing adjuvant therapy with tamoxifen
  • No concurrent use of other HDAC inhibitors
  • Palpable disease
  • Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
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  • Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed
  • No chemotherapy in the 14 days prior, or radiation therapy to index lesions in the thirty days prior to initiation of treatment on this study
  • No other concurrent chemotherapy; surgery or radiation therapy during the treatment phase of this protocol
  • No active major medical problems, including untreated or uncontrolled infections
  • No known CNS involvement by tumor
  • Patients must meet the following laboratory criteria:
  • Hematology:
  • Neutrophil count of >1500/mm3
  • Platelet count of > 100,000/mm3L
  • Hemoglobin ≥ 9 g/dL
  • 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
  • Total serum calcium (corrected for serum albumin) or ionized calcium ≥ LLN
  • Serum potassium ≥ LLN and ≤ HLN
  • Serum sodium ≥ LLN and ≤ HLN
  • Serum albumin ≥ LLN or 3g/dl
  • Patients with any elevated Alkaline Phosphatase due to bone metastasis can be enrolled
  • Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional normal.
  • TSH and free T4 within normal limits (patients may be on thyroid hormone replacement)
  • An echocardiogram > 50%
  • Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of study treatment. and must be willing to use two methods of contraception one of them being a barrier method during the study and for 3 months after last study drug administration

Who cannot join

  • Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer
  • Patients who will need valproic acid for any medical condition during the study or within 5 days prior to first panobinostat treatment
  • Impaired cardiac function including any one of the following:
  • Complete left bundle branch block or use of a permanent cardiac pacemaker, congenital long QT syndrome, history or presence of ventricular tachyarrhythmias, clinically significant resting bradycardia (<50 beats per minute), QTcF > 450 msec on screening ECG, or right bundle branch block + left anterior hemiblock (bifascicular block)
  • Presence of atrial fibrillation (ventricular heart rate >100 bpm)
  • Previous history angina pectoris or acute MI within 6 months
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  • Congestive heart failure (New York Heart Association functional classification III-IV) or baseline MUGA/Echo shows LVEF < 45%
  • Uncontrolled hypertension
  • Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix 1.-1)
  • Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)
  • Patients with unresolved diarrhea ≥ grade 2
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral panobinostat (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, obstruction, or stomach and/or small bowel resection)
  • Other concurrent severe and/or uncontrolled medical conditions
  • Patients who have received chemotherapy, any investigational drug or undergone major surgery < 4 weeks prior to starting study drug or who have not recovered from side effects of such therapy.
  • Concomitant use of any anti-cancer therapy or radiation therapy.
  • Women who are pregnant or breast feeding or women of childbearing potential (WOCBP) not willing to use a double barrier method of contraception during the study and 3 months after the end of treatment. One of these methods of contraception must be a barrier method. WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months). Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of the first administration of oral panobinostat.
  • Patients with a history of another primary malignancy within 5 years other than curatively treated CIS of the cervix, or basal or squamous cell carcinoma of the skin
  • Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis C; baseline testing for HIV and hepatitis C is not required
  • Patients with any significant history of non-compliance to medical regimens or with inability to grant a reliable informed consent
  • Unable to tolerate phlebotomy
  • Unable to tolerate biopsy
  • On any other hormonal or biological treatment drugs at the time of the study

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Tulane Cancer Center, Comprehensive Clinic, CTRC

    New Orleans, Louisiana, 70112

Other trials in United States

About this study

Official title: Pilot Study Evaluating the Expression of ERB-B4 After Treatment With HDAC Inhibitor in ER+ Tamoxifen Refractory Breast Cancer

The long-term objective of this research is to understand the molecular mechanisms of acquired endocrine resistance in breast cancer. Identifying these mechanisms is critical to the implementation of novel therapeutic strategies that can target and overcome altered gene networks involved in controlling breast cancer progression. While patients with tumors over expressing HER1, 2, or 3 have been shown to have reduced survival, patients with those tumors which overexpressed HER4 (erbB4) had increased survival (Witton 2003).

This is a non-randomized, single-arm, proof of principle trial. Selected are patients with advanced-stage breast cancer whose tumors are ER+, tamoxifen refractory. Histologically proven diagnosis of recurrent or metastatic breast cancer is advanced cancer for which there is no treatment available which would have a reasonable chance of cure. Treatment failure is defined as tumor progression after chemotherapy and tamoxifen therapy. Patients will be given five 30mg doses of HDAC inhibitor (LBH) over a period of two weeks. A dose will be taken on Days 1,3,5,8 and 10. Patients will have a diagnostic tumor biopsy prior to drug administration and a diagnostic biopsy within 48 hours (2 days) of the last dose. Primary endpoints are measured by biopsy of palpable tumor with immunohistochemical staining for ERBB4. Secondary end points include the evaluation of cell death, apoptosis, with immunohistochemical staining for DNA breaks by TUNEL assay.

Conditions
Breast Cancer
Being tested
Panobinostat (LBH589)
Keywords
estrogen receptor positive tamoxifen resistant breast cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Panobinostat (LBH589)Drug

    Patients will be given five 30mg doses of HDAC inhibitor (LBH) over a period of two weeks. A dose will be taken on Days 1,3,5,8 and 10. Patients will have a diagnostic tumor biopsy prior to drug administration and a diagnostic biopsy within 48 hours (2 days) of the last dose.

Study groups in NCT00993642
Study groupRoleWhat they receive
All ParticipantsExperimentalNot described
Receives: Drug: Panobinostat (LBH589)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The primary objective of the study is to compare the expression level of ERBB4 pre- and post- treatment with HDACi, Panobinostat (LBH589).

    Measured: 2 week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Oct 2009 (estimated)
  2. Study startSep 2009
  3. Primary completionSep 2010
  4. Study completionDec 2010

Why it stopped: Lack of accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00993642
Sponsor's protocol ID
CLBH589BUS46T
Other IDs
CLBH589BUS46T
Status last verified
Mar 2017
First submitted
9 Oct 2009
Last updated
13 Mar 2017
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Panobinostat (LBH589) in people with Breast Cancer, run by Tulane University Health Sciences Center 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 29 inclusion and 22 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: withdrawn, as of the sponsor's last update on 13 Mar 2017. 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?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

The primary objective of the study is to compare the expression level of ERBB4 pre- and post- treatment with HDACi, Panobinostat (LBH589). (time frame: 2 week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00993642.

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 13 Mar 2017.

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