Clinical trial NCT00993642 (early phase 1, status: withdrawn)
Conditions: breast cancer
ICD codes: C79.81, D24.1, D24.2, D24.9, D49.3, C44.501, D48.60
Drugs: panobinostat (lbh589)
SMILES: [H]\C(=C(\[H])C1=CC=C(CNCCC2=C(C)NC3=CC=CC=C23)C=C1)C(O)=NO
Reason stopped: 
    lack of accrual
  
Eligibility criteria:

        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
                  enrolled

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

         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
             1.-1)

          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 skin

         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