Trial of LBH589 in Metastatic Thyroid Cancer

University of Wisconsin (UW)

Status and phase

Completed

Phase 2

Conditions

Thyroid Carcinoma

Treatments

Drug: LBH589

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT01013597

CO08322 (Other Identifier)

NCI-2011-00715 (Registry Identifier)

H-2009-0173 (Other Identifier)

A534260 (Other Identifier)

SMPH\MEDICINE\HEM-ONC (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

13 patients

Sex

All

Ages

18+ years old

Volunteers

No 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