Trial of LBH589 in Metastatic Thyroid Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01013597
First received: October 28, 2009
Last updated: September 26, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Thyroid Carcinoma
Drug: LBH589
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of LBH589 in Patients With Metastatic Medullary Thyroid Cancer and Radioactive Iodine Resistant Differentiated Thyroid Cancer

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Tumor response rate to LBH589. [ Time Frame: Every 8 weeks. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Protein expression patterns of Notch1 in thyroid tissue samples. [ Time Frame: End of study ] [ Designated as safety issue: No ]
  • Time to progression of thyroid cancer [ Time Frame: Yearly ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Yearly ] [ Designated as safety issue: No ]
  • Impact of LBH589 on tumor markers for thyroid cancer [ Time Frame: Yearly ] [ Designated as safety issue: No ]
  • Toxicity of LBH589 [ Time Frame: Every 4 weeks. ] [ Designated as safety issue: Yes ]
  • Tolerability of LBH589 [ Time Frame: Every 4 weeks. ] [ Designated as safety issue: No ]

Estimated Enrollment: 33
Study Start Date: January 2010
Estimated Study Completion Date: August 2014
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LBH589 Drug: LBH589
LBH589 20mg by mouth three times weekly (Monday/Wednesday/Friday) for 28-day cycles.
Other Name: panobinostat

Detailed Description:

Medullary thyroid cancer (MTC) is a neuroendocrine tumor and accounts for 3-5% of cases of thyroid cancer. The majority of patients with MTC do not present with early stage disease. Differentiated thyroid cancer (DTC) accounts for >90% of all thyroid cancers. In a sub-set of patients, thyroid cells become resistant to I-131 radioiodine therapy and subsequently develop distant metastases. In both MTC and DTC, systemic chemotherapy for metastatic disease is largely ineffective.

LBH589 is a histone deacetylase (HDAC) with recently demonstrated activity to inhibit the Notch1 signaling pathway in MTC cancer cells and suppress tumor cell proliferation in DTC cancer cells. This clinical trial will evaluate the tumor response rate of LBH589 in patients with metastatic MTC or radioactive iodine resistant DTC.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01013597

Locations
United States, Wisconsin
St. Vincent Regional Cancer Center CCOP
Green Bay, Wisconsin, United States, 54301
University of Wisconsin - Madison
Madison, Wisconsin, United States, 53792
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
University of Wisconsin, Madison
Novartis Pharmaceuticals
Investigators
Principal Investigator: Anne Traynor, M.D. University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT01013597     History of Changes
Other Study ID Numbers: H-2009-0173, CO 08322
Study First Received: October 28, 2009
Last Updated: September 26, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Wisconsin, Madison:
thyroid
medullary
differentiated
radioiodine-resistant
LBH589
panobinostat

Additional relevant MeSH terms:
Thyroid Diseases
Thyroid Neoplasms
Endocrine System Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Panobinostat
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 16, 2014