A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer

Conditions
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Anaplastic Thyroid Cancer, Thyroid Cancer

Intervention / Treatment
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* Drug: MLN0128


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MLN0128<br>Treatment will be administered on an outpatient basis. MLN0128 at fixed dose will be administered orally, daily for treatment cycle. The participant will be requested to maintain a medication diary of medication. The medication diary will be returned to clinic staff at the end of each cycle. Treatment with MLN0128 will continue until progression or withdrawal of consent. | Drug: MLN0128<br>* This is a non-randomized phase II study to investigate efficacy of MLN0128 in metastatic anaplastic thyroid cancer cases.<br>* Other names: INK128;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | baseline, 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall All Response Rate |  | 2 Years | 
| Overall Survival Rate |  | 2 Years | 
| Number of Participants with Serious and Non-Serious Adverse Events |  | 2 Years | 
| • Identification of biomarkers predictive of response to therapy with MLN0128 |  | 2 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaplastic Thyroid Cancer, Thyroid Cancer