A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer
A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer
This research study is studying a targeted therapy (ML0N128) as a possible treatment for
 anaplastic thyroid cancer.

 This research study is a Phase II clinical trial. Phase II clinical trials test the safety
 and effectiveness of an investigational intervention to learn whether the intervention works
 in treating a specific disease. "Investigational" means that the intervention is being
 studied. The FDA (the U.S. Food and Drug Administration) has not approved MLN0128 as a
 treatment for any disease.

 MLN0128 prevents tumor cells from dividing and growing by selectively and potently inhibiting
 a chemical, mTOR kinase, which regulates cell growth and survival. Patients with anaplastic
 thyroid cancer have been observed to sometimes carry genetic alterations in their tumor cells
 which may make the cancer more sensitive to inhibition by MLN0128.

 In this research study,the investigators are investigating usefulness of MLN0128 in
 metastatic anaplastic thyroid cancer cases.
Patients who fulfill eligibility criteria will be entered into the trial to receive ML0N128.
 The participant will be given a study drug-dosing diary for each treatment cycle. After the
 screening procedures confirm participation in the research study.

 - MLN0128 - Fixed doses daily per treatment cycle

 The treatment cycles will continue until the participants disease gets worse or is taken off
 treatment for any other reason.Once treatment has been discontinued the investigators will
 check on the participants health status by phone for the rest of their life.
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

 Exclusion Criteria:

 -  Female patients who are both lactating and breastfeeding or have a positive serum
 pregnancy test during the screening period

 -  Any serious medical or psychiatric illness that could, in the investigator's opinion,
 potentially interfere with the completion of treatment

 -  Treatment with any investigational products within 14 days

 -  Failed to recover from the reversible effects of prior anticancer therapies

 -  Manifestations of malabsorption due to prior gastrointestinal surgery or disease

 -  Poorly controlled diabetes mellitus

 -  History of any of the following within the last 6 months prior to study entry:

 -  Ischemic myocardial event

 -  Ischemic cerebrovascular event

 -  Requirement for inotropic support (excluding digoxin) or serious (uncontrolled)
 cardiac arrhythmia

 -  Placement of a pacemaker for control of rhythm

 -  New York Heart Association Class III or IV heart failure

 -  Pulmonary embolism

 -  Significant active cardiovascular or pulmonary disease at the time of study entry,
 including:

 -  Uncontrolled high blood pressure

 -  Pulmonary hypertension

 -  Uncontrolled asthma or O2 saturation < 90%

 -  Significant valvular disease

 -  Medically significant (symptomatic) bradycardia

 -  History of arrhythmia requiring an implantable cardiac defibrillator

 -  Baseline prolongation of the rate-corrected QT interval (QTc)

 -  Treatment with hematopoietic growth factors, transfusions of blood and blood products,
 or systemic corticosteroids