A Phase II Trial of CUDC-907 in Patients With Metastatic and Locally Advanced Thyroid Cancer

Background: * There are no standard or effective systemic therapies for metastatic or locally advanced poorly differentiated and undifferentiated thyroid cancer. * Poorly differentiated and undifferentiated thyroid cancer are aggressive, with high mortality. * CUDC-907 is a first-in-class dual inhibitor of histone deacetylase (HDAC) and PI3K signaling. * Approximately 80% of poorly differentiated and undifferentiated thyroid cancers have driver mutations in the PI3K/AKT pathway or activation of the pathway. * HDAC2 is upregulated in poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer, and CUDC-907 treatment reduces HDAC2 levels in thyroid cancer cells. * CUDC-907 inhibits thyroid cancer cell growth, invasion and migration in vitro. * In addition to inhibiting the PI3K/AKT signaling pathway, CUDC-907 inhibits the EGFR/RAS/RAF/MEK/ERK signaling pathway, which is also activated in poorly differentiated and undifferentiated thyroid cancer. * CUDC-907 inhibits growth and metastases in a mouse model of metastatic thyroid cancer. * We hypothesize that CUDC-907 will cause cancer regression in patients with metastatic and locally advanced poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer. Objective: -To determine response to CUDC-907 treatment by Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with locally advanced and metastatic poorly differentiated and undifferentiated thyroid cancer, and aggressive variants of differentiated thyroid cancer. Eligibility: * Age greater than or equal to 18 years * Thyroid cancer that is refractory to or relapsed after standard treatment. * Aggressive thyroid cancer confirmed on histology or cytologic analysis. * Measurable disease. * Last dose of chemotherapy or last radiotherapy treatment more than 4 weeks prior to starting treatment with this protocol, except for subjects with anaplastic/undifferentiated thyroid cancer who may enroll immediately after discontinuation of previous therapy. Design: * Open label, phase II trial to determine response to CUDC-907 treatment. * Patients will be given 60 mg of CUDC-907 orally for 5 consecutive days followed by 2 days off (5/2 schedule). * One cycle is 21 days. Patients may continue on treatment if there is no disease progression. * Initial anatomic and functional imaging will be performed at enrollment and after 2 cycles of treatment. Thereafter, anatomic imaging will be performed every two cycles of treatment.