CUDC-907 Treatment in People With Metastatic and Locally Advanced Thyroid Cancer
Condition: Thyroid Neoplasms; Poorly Differentiated and Undifferentiated Thyroid Cancer; Differentiated Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Thyroid Diseases
Intervention: CUDC-907
Intervention description: 60 mg (2 capsules of 30 mg capsules) will be given orally once a day 5 days on and 2 days off.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a single group assignment. All patients regardless of subtype of thyroid cancer received one single treatment and follow up plan with option to continue the treatment when scan was negative.
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Dual Inhibitor of HDAC and P13K Signaling; HDAC2; EGFR/RAS/RAF/MEK/ERK Signaling Pathway Inhibition

Summary:

      Background:

      The thyroid is a gland at the base of the throat. Thyroid cancer is a disease that people get
      when abnormal cells begin to grow in this gland. Researchers believe a new drug called
      CUDC-907 may be able to help people with thyroid cancer that has spread or has gotten worse.

      Objective:

      To see if CUDC-907 will shrink tumors in people with advanced thyroid cancer.

      Eligibility:

      People at least 18 years old who have been diagnosed with locally advanced and metastatic
      thyroid cancer.

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Blood and urine tests

      Electrocardiogram (ECG) heart test.

      Review of their symptoms and how they perform normal activities

      A scan will be performed. Some will have a computed tomographic scan (CT) that takes pictures
      of the body using a small amount of radiation. Some will have magnetic resonance imaging
      (MRI) that uses a magnetic field to take pictures.

      Bone scan (some participants)

      Fludeoxyglucose (FDG) positron emission tomography (PET) scan to produce a tumor image.

      A sample of their tumor from a previous surgery. They may have a biopsy of their tumor if a
      tumor sample is not available from a previous surgery.

      Participants will be given CUDC-907 in tablet form. They will take it by mouth once a day for
      5 days, then take 2 days off, each week.

      While taking the study drug, participants will have study visits that repeat the screening
      tests.

      After they stop treatment, participants will have 3 follow-up visits over a year. They will
      repeat some tests. Then participants will be contacted by phone or e-mail every 6 months....
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Subjects greater than or equal to 18 years of age.

          -  Thyroid cancer histology or cytology that is aggressive (anaplastic/undifferentiated
             thyroid cancer, poorly differentiated thyroid cancer, Hurthle cell carcinoma,
             tall-cell variant of papillary thyroid cancer, sclerosing variant of papillary thyroid
             cancer).

          -  Measurable disease.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          -  Absolute neutrophil count greater than or equal to 1,000/microL

          -  Platelets greater than or equal to 75,000/microL

          -  Creatinine less than or equal to 1.5 times upper limit of normal (ULN) or creatinine
             clearance > 60ml for patients with creatinine levels 1.5 times above institutional ULN
             (calculated based on age, weight and sex

          -  Total bilirubin less than or equal to 1.5 times ULN; aspartate aminotransferase
             (AST)/alanine aminotransferase (ALT) less than or equal to 2.5 times ULN. For subjects
             with documented liver metastases, the AST/ALT may be less than or equal to 5 times
             ULN.

          -  Recovery to Grade 1 or baseline of any toxicity due to prior anticancer therapies
             (excluding alopecia).

          -  Platelet transfusions to help patients meet eligibility criteria are not allowed
             within 3 days prior to screening complete blood count (CBC) or Cycle 1, Day 1
             treatment.

          -  Women of child bearing potential must have a negative serum pregnancy test.

          -  The effects of CUDC-907 on the developing human fetus are unknown. For this reason,
             women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry, for
             the duration of study participation and for 30 days following the last study
             treatment.

        Should a woman become pregnant or suspect she is pregnant while she or her partner is
        participating in this study, she should inform her treating physician immediately.

        -Able to provide written informed consent and to follow protocol requirements.

        EXCLUSION CRITERIA:

          -  Systemic anticancer therapy within 4 weeks of study entry, except for subjects with
             anaplastic/undifferentiated thyroid cancer who may be enrolled immediately after
             discontinuation of previous therapy.

          -  Other investigational agents within 4 weeks prior to study treatment except for
             subjects with anaplastic/undifferentiated thyroid cancer who may be enrolled
             immediately of discontinuation of previous therapy.

          -  Pregnant women are excluded from this study because the potential risk of teratogenic
             or abortifacient effects of CUDC-907 is unknown. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with CUDC-907, breastfeeding should be discontinued if the mother is treated
             with CUDC-907. These potential risks may also apply to other agents used in this
             study.

          -  Diabetes mellitus that is not controlled with medication.

          -  Serious infection requiring intravenous antibiotic therapy within 14 days prior to
             study treatment.

          -  Evidence of central nervous system metastasis.

          -  Uncontrolled or severe cardiovascular disease, including myocardial infarction,
             unstable angina, or atrial fibrillation (AFib) within 6 months prior to study
             treatment, New York Heart Association (NYHA) Class II or greater congestive heart
             failure, serious arrhythmias requiring medication for treatment, clinically
             significant pericardial disease, cardiac amyloidosis, or corrected QT interval (QTc)
             with Fridericia's (QTcF) correction that is unmeasurable or greater than or equal to
             480 msec on screening electrocardiogram (ECG). (Note: for QTcF greater than or equal
             to 480 sec on the screening ECG, the ECG may be repeated twice at least 24 hours
             apart; the mean QTcF from the three screening ECGs must be < 480 msec in order to meet
             eligibility for trial participation).

          -  Gastrointestinal disease or disorder that could interfere with the swallowing, oral
             absorption, or tolerance of CUDC-907. This includes uncontrolled diarrhea (> 1 watery
             stool/day), major abdominal surgery, significant bowel obstruction and/or
             gastrointestinal diseases that could alter the assessment of pharmacokinetics or
             safety, including but not limited to: irritable bowel syndrome, ulcerative colitis,
             Crohn's disease and hemorrhagic coloproctitis.

          -  Unstable or clinically significant concurrent medical condition that would, in the
             opinion of the investigator, jeopardize the safety of a subject and/or compliance with
             the protocol.

          -  Second primary malignancy within 2 years of study entry other than adequately treated
             non-melanoma skin or superficial bladder cancer, curatively treated carcinoma in situ
             of the cervix or other curatively treated solid tumor deemed by the investigator to be
             at low risk for recurrence.