Trial of LBH589 in Metastatic Thyroid Cancer
Condition: Thyroid Carcinoma
MeSH terms: Thyroid Neoplasms; Thyroid Diseases
Intervention: LBH589
Intervention description: LBH589 20mg by mouth three times weekly (Monday/Wednesday/Friday) for 28-day cycles.
Intervention MeSH terms: Panobinostat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 13.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: thyroid; medullary; differentiated; radioiodine-resistant; LBH589; panobinostat

Summary:

      The purpose of this study is to evaluate the tumor response rate in patients with metastatic
      medullary thyroid cancer (MTC) or radioiodine resistant differentiated thyroid cancer (DTC)
      after receiving treatment with LBH589 20 mg by mouth, three times weekly. Time to
      progression, overall survival, toxicity, tolerability, and Notch1 protein expression patterns
      will also be evaluated.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed metastatic medullary or differentiated thyroid cancer.
             Diagnosis must be confirmed at University of Wisconsin

          -  Patients must have measurable disease as defined by RECIST.

          -  At least 3 weeks from the completion of major surgery, chemotherapy, or other systemic
             therapy or local liver therapy to study registration

          -  No concurrent chemotherapy or radiation therapy

          -  ECOG Performance Status of ≤ 2

          -  Ability to provide written informed consent obtained prior to participation in the
             study and any related procedures being performed

          -  Adequate bone marrow, kidney, liver function

          -  Left ventricular ejection fraction ≥ the lower limit of the institutional normal

          -  Those with differentiated thyroid cancer must have radioactive iodine resistant
             disease, defined by failure to incorporate 131-Iodine after therapy, FDG-avidity on a
             PET scan, or progression of measurable disease after 131-Iodine therapy or an allergy
             to radioactive iodine

          -  Hypertension must be well controlled (to less than 150/90 mmHg) on a stable regimen of
             anti-hypertensive therapy

        Exclusion Criteria:

          -  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 LBH589 treatment

          -  Impaired cardiac function

          -  Concomitant use of drugs with a risk of causing torsades de pointes

          -  Patients with unresolved diarrhea > CTCAE grade 1

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of oral LBH589

          -  Other concurrent severe and/or uncontrolled medical conditions

          -  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 last study drug administration. Women of childbearing potential must have
             a negative serum pregnancy test within 7 days of the first administration of oral
             LBH589.

          -  Male patients whose sexual partners are WOCBP not using a double method of
             contraception during the study and 3 months after the end of treatment

          -  Patients with a history of another primary malignancy that, in the opinion of the
             investigator, would interfere with the assessment of the primary endpoints of the
             study

          -  Patients with known positivity for human immunodeficiency virus (HIV) or hepatitis C

          -  Patients with any significant history of non-compliance to medical regimens or with
             inability to grant a reliable informed consent