Cyclophosphamide and Sirolimus for the Treatment of Metastatic, RAI-refractory, Differentiated Thyroid Cancer

Inclusion Criteria: * Histologically documented differentiated thyroid cancer with or without metastases, not amenable to curative treatment; or the patient has documented refusal of curative treatment * Measurable disease (\>10 mm) and have progression of disease based on RECIST criteria. Previously irradiated tumor lesions are not considered measurable unless they have progressed since radiation. * Previous failure of Iodine-131 (131I) therapy or not candidates to receive 131I as assessed by treating physician. * Age ≥ 18 years * ECOG (Eastern Cooperative Oncology Group) performance status 0-2 * Life expectance of ≥ 12 weeks * 131I therapy not allowed within 24 weeks before entry (4 weeks if negative post-treatment scan) * Adequate organ and marrow function * Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment * Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment * Willingness and ability to comply with scheduled visits, treatment plans, including willingness to take study medication, laboratory tests, and other study procedures Exclusion Criteria: * Inability to obtain Foundation One testing on archival tissue, or, lack of previous Next Generation Sequencing * Chemotherapy, tyrosine kinase inhibitor, or radiation therapy within 4 weeks * Prior experimental therapy within 4 we…