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

Phase 0
18 Years
Not Enrolling
Breast Cancer

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Trial Information

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

Inclusion Criteria:

1. Patient age is ≥ 18 years

2. Female

3. 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

4. No concurrent use of other HDAC inhibitors

5. Palpable disease

6. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

7. Ability to provide written informed consent obtained prior to participation in the
study and any related procedures being performed

8. 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

9. No other concurrent chemotherapy; surgery or radiation therapy during the treatment
phase of this protocol

10. No active major medical problems, including untreated or uncontrolled infections

11. No known CNS involvement by tumor

12. 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

13. Baseline MUGA or ECHO must demonstrate LVEF ≥ the lower limit of the institutional

14. TSH and free T4 within normal limits (patients may be on thyroid hormone replacement)

15. An echocardiogram > 50%

16. 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

Exclusion Criteria:

1. Prior HDAC, DAC, HSP90 inhibitors or valproic acid for the treatment of cancer

2. Patients who will need valproic acid for any medical condition during the study or
within 5 days prior to first panobinostat treatment

3. 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

- Congestive heart failure (New York Heart Association functional classification
III-IV) or baseline MUGA/Echo shows LVEF < 45%

4. Uncontrolled hypertension

5. Concomitant use of drugs with a risk of causing torsades de pointes (See Appendix

6. Concomitant use of CYP3A4 inhibitors (See Appendix 1.-2)

7. Patients with unresolved diarrhea ≥ grade 2

8. 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)

9. Other concurrent severe and/or uncontrolled medical conditions

10. 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.

11. Concomitant use of any anti-cancer therapy or radiation therapy.

12. 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.

13. 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

14. Patients with known positivity for human immunodeficiency virus (HIV) ) or hepatitis
C; baseline testing for HIV and hepatitis C is not required

15. Patients with any significant history of non-compliance to medical regimens or with
inability to grant a reliable informed consent

16. Unable to tolerate phlebotomy

17. Unable to tolerate biopsy

18. On any other hormonal or biological treatment drugs at the time of the study

Type of Study:


Study Design:

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Outcome Measure:

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

Outcome Time Frame:

2 week

Safety Issue:


Principal Investigator

Bridgette Collins-Burow, MD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Tulane Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

September 2009

Completion Date:

December 2010

Related Keywords:

  • Breast Cancer
  • estrogen receptor positive tamoxifen resistant breast cancer
  • Breast Neoplasms



Tulane Cancer Center, Comprehensive Clinic, CTRC New Orleans, Louisiana  70112