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Trial of LBH589 in Metastatic Thyroid Cancer

Primary Purpose

Thyroid Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
LBH589
Sponsored by
University of Wisconsin, Madison
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Thyroid Carcinoma focused on measuring thyroid, medullary, differentiated, radioiodine-resistant, LBH589, panobinostat

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • St. Vincent Regional Cancer Center CCOP
  • University of Wisconsin - Madison
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LBH589

Arm Description

Outcomes

Primary Outcome Measures

Tumor Response Rate to LBH589.
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).)

Secondary Outcome Measures

Protein Expression Patterns of Notch1 in Thyroid Tissue Samples.
Time to Progression of Thyroid Cancer
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
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
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
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
Tolerability and toxicity were not assessed separately, therefore tolerability is reported as toxicity.

Full Information

First Posted
October 28, 2009
Last Updated
November 14, 2019
Sponsor
University of Wisconsin, Madison
Collaborators
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT01013597
Brief Title
Trial of LBH589 in Metastatic Thyroid Cancer
Official Title
A Phase II Trial of LBH589 in Patients With Metastatic Medullary Thyroid Cancer and Radioactive Iodine Resistant Differentiated Thyroid Cancer
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
February 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
Novartis Pharmaceuticals

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thyroid Carcinoma
Keywords
thyroid, medullary, differentiated, radioiodine-resistant, LBH589, panobinostat

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
13 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LBH589
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
LBH589
Other Intervention Name(s)
panobinostat
Intervention Description
LBH589 20mg by mouth three times weekly (Monday/Wednesday/Friday) for 28-day cycles.
Primary Outcome Measure Information:
Title
Tumor Response Rate to LBH589.
Description
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).)
Time Frame
Every 8 weeks.
Secondary Outcome Measure Information:
Title
Protein Expression Patterns of Notch1 in Thyroid Tissue Samples.
Time Frame
End of study
Title
Time to Progression of Thyroid Cancer
Description
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.
Time Frame
Every 3 months until progression up to 5 years
Title
Overall Survival
Description
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.
Time Frame
Every 3 months up to 5 years
Title
Impact of LBH589 on Tumor Markers for Thyroid Cancer
Description
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.
Time Frame
Baseline and end of treatment, up to 1 year
Title
Toxicity of LBH589
Description
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.
Time Frame
Every 4 weeks, up to 5 years
Title
Tolerability of LBH589
Description
Tolerability and toxicity were not assessed separately, therefore tolerability is reported as toxicity.
Time Frame
Every 4 weeks, up to 5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Traynor, M.D.
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
St. Vincent Regional Cancer Center CCOP
City
Green Bay
State/Province
Wisconsin
ZIP/Postal Code
54301
Country
United States
Facility Name
University of Wisconsin - Madison
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53792
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Links:
URL
https://cancer.wisc.edu/
Description
University of Wisconsin Carbone Cancer Center

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Trial of LBH589 in Metastatic Thyroid Cancer

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