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 ofcurative treatment

• Measurable disease (>10 mm) and have progression of disease based on RECISTcriteria. Previously irradiated tumor lesions are not considered measurable unlessthey have progressed since radiation.

• Previous failure of Iodine-131 (131I) therapy or not candidates to receive 131I asassessed 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 negativepost-treatment scan)

• Adequate organ and marrow function

• Women of childbearing potential must have a negative serum or urine pregnancy testwithin 3 days prior to treatment

• Signed and dated informed consent document indicating that the patient (or legallyacceptable representative) has been informed of all pertinent aspects of the trialprior to enrollment

• Willingness and ability to comply with scheduled visits, treatment plans, includingwillingness to take study medication, laboratory tests, and other study procedures

Exclusion Criteria:

• Inability to obtain Foundation One testing on archival tissue, or, lack of previousNext Generation Sequencing

• Chemotherapy, tyrosine kinase inhibitor, or radiation therapy within 4 weeks

• Prior experimental therapy within 4 weeks of planned start of this trial

• 131I therapy within 24 weeks before entry (4 weeks if negative post-treatment scan)

• Previous treatment with an mTOR inhibitor

• Patients who are currently receiving treatment with strong inhibitors or inducers ofCYP3A4 or P-glycoprotein that cannot be discontinued at least one week prior to thestart of treatment with Cyclophosphamide and Sirolimus

• Impairment of GI (gastrointestinal) function or GI disease that may significantlyalter the absorption of study medications (e.g., ulcerative diseases, uncontrollednausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection) includingdependence on a G-Tube for administration of medications.

• A serious uncontrolled medical disorder or active infection that would impair theirability to receive study treatment

• Patients with known sensitivities to either cyclophosphamide and/or sirolimus

• Patients with known urinary outflow obstruction

• Dementia or significantly altered mental status that would prohibit theunderstanding or rendering of informed consent and compliance with the requirementsof this protocol

• Patients (male and female) having procreative potential who are not willing or notable to use adequate contraception or practicing abstinence

• Women who are pregnant or breast-feeding

• Patients residing in prison