Trial of LBH589 in Metastatic Thyroid Cancer
|ClinicalTrials.gov Identifier: NCT01013597|
Recruitment Status : Completed
First Posted : November 13, 2009
Results First Posted : July 11, 2016
Last Update Posted : April 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|Thyroid Carcinoma||Drug: LBH589||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Trial of LBH589 in Patients With Metastatic Medullary Thyroid Cancer and Radioactive Iodine Resistant Differentiated Thyroid Cancer|
|Study Start Date :||January 2010|
|Actual Primary Completion Date :||August 2013|
|Actual Study Completion Date :||February 2016|
LBH589 20mg by mouth three times weekly (Monday/Wednesday/Friday) for 28-day cycles.
Other Name: panobinostat
- Tumor Response Rate to LBH589. [ Time Frame: Every 8 weeks. ]per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v.1.0) for target lesions and assessed by CT/MRI: "Response" includes Complete Response (CR, disappearance of all target lesions), or Partial Response (PR, >=30% decrease in the sum of the longest diameter of target lesions). "No Response" includes Stable Disease (SD, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease), and Progressive Disease (PD, at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum longest diameter recorded since the baseline measurements, or the appearance of one or more new lesion(s).)
- Protein Expression Patterns of Notch1 in Thyroid Tissue Samples. [ Time Frame: End of study ]
- Time to Progression of Thyroid Cancer [ Time Frame: Every 3 months until progression up to 5 years ]Progression is defined using the Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Time to progression is defined as the number of days from the day of first LBH589 administration to the day the patient experienced an event of disease progression or death, whichever came first. Progression was assessed every 3 months until death or up to 5 years, whichever occurred first.
- Overall Survival [ Time Frame: Every 3 months up to 5 years ]For a given patient, overall survival (OS) is defined as the number of days from the day of first LBH589 administration until the patient's death. If a patient was alive at the time of analysis, then the patient's data is censored at the date of the last available evaluation.Survival was assessed every three months until death or final data analysis, whichever occurred first.
- Impact of LBH589 on Tumor Markers for Thyroid Cancer [ Time Frame: Baseline and end of treatment, up to 1 year ]Change in serum Thyroglobulin level from baseline to end of treatment. Treatment continued until either extraordinary medical circumstances, disease progression, toxicity, subject withdrawal, or death. At the time subjects came off of study treatment for one of the reasons already listed, a sample was collected for tumor markers.
- Toxicity of LBH589 [ Time Frame: Every 4 weeks, up to 5 years ]Most frequent toxicities at least possibly related to panobinostat, grades 2-4 (grading based on NCI common terminology criteria for adverse events CTCAE version 3). Toxicities were collected from the time the patient provided informed consent until 4 weeks after the patient stopped LBH589.
- Tolerability of LBH589 [ Time Frame: Every 4 weeks, up to 5 years ]Tolerability and toxicity were not assessed separately, therefore tolerability is reported as toxicity.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01013597
|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|
|Principal Investigator:||Anne Traynor, M.D.||University of Wisconsin, Madison|