Clinical trial NCT01013597: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Thyroid Carcinoma
Keywords: thyroid
medullary
differentiated
radioiodine-resistant
LBH589
panobinostat
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: Novartis Pharmaceuticals
First posted: 2009-11-13
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Tumor Response Rate to LBH589.
timeFrame: Every 8 weeks.
Secondary outcomes:
measure: Protein Expression Patterns of Notch1 in Thyroid Tissue Samples.
timeFrame: End of study
measure: Time to Progression of Thyroid Cancer
timeFrame: Every 3 months until progression up to 5 years
measure: Overall Survival
timeFrame: Every 3 months up to 5 years
measure: Impact of LBH589 on Tumor Markers for Thyroid Cancer
timeFrame: Baseline and end of treatment, up to 1 year
measure: Toxicity of LBH589
timeFrame: Every 4 weeks, up to 5 years
measure: Tolerability of LBH589
timeFrame: Every 4 weeks, up to 5 years
Other outcomes:
Locations:
city: Green Bay
country: United States
facility: St. Vincent Regional Cancer Center CCOP
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin - Madison
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Anne Traynor, M.D.
role: PRINCIPAL_INVESTIGATOR
References: