A Phase I/II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer and Incurably Poorly Differentiated or Radioidodine Refractory Differentiated Thyroid Cancer

Inclusion Criteria

• •Male or female patients 18 years or older
• •Any number of prior chemotherapy or targeted agents including rapamycin analogues allowed
• •Newly diagnosed or refractory/metastatic anaplastic thyroid cancer confirmed by histology, incurable by surgery, radiotherapy or chemoradiotherapy alone or in combination
• •Must have measurable disease
• •ECOG performance status 0-2
• •No active intracranial metastases
• •Tissue for correlative studies must be available
• •Ability to swallow oral medications
• •Voluntary written consent must be given before performance of any study related procedure
• •Adequate organ function, as specified below, within 21 days:
• •* Bone marrow reserve consistent with: absolute neutrophil count (ANC) ≥ 1.5 x 109/L; platelet count ≥ 100 x 109/L; hemoglobin ≥ 9 g/dL;
• •* Hepatic: total bilirubin ≤1.5 x upper limit of normal (ULN), transaminases (aspartate aminotransferase/serum glutamic oxaloacetic transaminase-AST/SGOT and alanine aminotransferase/serum glutamic pyruvic transaminase-ALT/SGPT) ≤2.5 x ULN (≤5 x ULN if liver metastases are present);
• •* Renal: creatinine clearance ≥50 mL/min
• •* Metabolic: fasting serum glucose (≤ 130 mg/dL) and fasting triglycerides ≤ 300 mg/dL
• •* Left ventricular ejection fraction (LVEF) within 5 absolute percentage points of institutional standard of normal as measured by echocardiogram (ECHO) or multiple gated acquisition scan (MUGA) within 4 weeks prior to first study drug administration (ie, if the institutional normal is 50%, subject's LVEF may be as low as 45% to be eligible for the study)
• •Female patients who:
• •* Are postmenopausal for at least 1 year before the screening visit, OR
• •* Are surgically sterile, OR
• •* If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study drug, or agree to completely abstain from heterosexual intercourse
• •Male patients, even if surgically sterilized (ie, status post-vasectomy), who:
• •* Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, or
• •* Agree to completely abstain from heterosexual intercourse
• •Treatment with strong CYP2C19, CYP3A4, and CYP2C9 inhibitors and/or inducers must be discontinued