Clinical Trials /

A Phase II Study of MLN0128 in Metastatic Anaplastic Thyroid Cancer

NCT02244463

Description:

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.

Related Conditions:
  • Thyroid Gland Undifferentiated (Anaplastic) Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: 14-223
  • NCT ID: NCT02244463

Conditions

  • Anaplastic Thyroid Cancer
  • Thyroid Cancer

Interventions

DrugSynonymsArms
MLN0128INK128MLN0128

Purpose

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

      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.
    

Trial Arms

NameTypeDescriptionInterventions
MLN0128ExperimentalTreatment 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.
  • MLN0128

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression Free Survival
Time Frame:baseline, 4 months
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Anaplastic Thyroid Cancer
  • Thyroid Cancer

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