Inolitazone Dihydrochloride and Paclitaxel in Treating Patients With Advanced Anaplastic Thyroid Cancer
Condition: Anaplastic Thyroid Cancer; Recurrent Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Thyroid Diseases
Intervention: efatutazone; paclitaxel
Intervention description: Given PO; Given IV
Intervention MeSH terms: Paclitaxel; Efatutazone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well inolitazone dihydrochloride (efatutazone
      dihydrochloride) and paclitaxel work in treating patients with anaplastic thyroid cancer that
      has spread to other places in the body and usually cannot be cured or controlled with
      treatment (advanced). Drugs used in chemotherapy, such as efatutazone dihydrochloride and
      paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading.
    

Eligibility criteria:

        -  Patients must have histologically or cytologically diagnosed advanced anaplastic
             thyroid cancer (ATC)

          -  Patients must have measurable disease

          -  Patients must have either metastatic (stage IVC) or locally advanced unresectable
             disease (stage IVB)

          -  Patients should have resolution of any toxic effects of prior therapy (except
             alopecia) to National Cancer Institute (NCI) Common Terminology Criteria for Adverse
             Events (CTCAE), version 4.0, grade 1

          -  There is no limit to the number of prior lines of treatment a patient has received

          -  No treatment with chemotherapy, radiation therapy, immunotherapy, biological therapy,
             hormonal therapy, or other thiazolidinediones (TZDs) =< 21 days before study
             registration

          -  No prior taxane therapy =< 6 months, except as a radiosensitizer

          -  No history of the following:

               -  Class III or IV congestive heart failure (CHF)

               -  Grade 3 or 4 thromboembolic event =< 6 months

               -  Pericardial effusion =< 12 months (any grade)

               -  Pericardial involvement with tumor

               -  Grade 2 or higher pleural effusion =< 6 months

          -  No current symptomatic, untreated, or uncontrolled brain metastases present

          -  No major surgery =< 14 days prior to registration

          -  No grade 2 or higher neuropathy

          -  No known history of severe hypersensitivity reactions to any of the components of
             efatutazone or paclitaxel formulations

          -  Not pregnant and not nursing; women of childbearing potential only, a negative
             pregnancy test done =< 7 days prior to registration is required

          -  Patients with diabetes mellitus requiring concurrent treatment with insulin or
             thiazolidinedione (TZD) oral agents are not eligible

          -  Patients with known hypersensitivity to any TZD oral agents are not eligible

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Creatinine =< 1.5 x upper limit of normal (ULN) mg/dL OR calculated (calc.) creatinine
             clearance >= 60 mL/min

          -  Bilirubin =< 1.5 x ULN

          -  Aspartate aminotransferase (AST) =< 2.5 x ULN

          -  Although they will not be considered formal eligibility (exclusion) criteria,
             physicians should recognize that the following may seriously increase the risk to the
             patient entering this protocol:

               -  Psychiatric illness which would prevent the patient from giving informed consent

               -  Medical condition such as uncontrolled infection (including human
                  immunodeficiency virus [HIV]), uncontrolled diabetes mellitus or cardiac disease
                  which, in the opinion of the treating physician, would make this protocol
                  unreasonably hazardous for the patient

               -  Patients with a "currently active" second malignancy other than non-melanoma skin
                  cancers; patients are not considered to have a "currently active" malignancy if
                  they have completed therapy and are free of disease for >= 3 years; there is an
                  exception for patients with a history of well differentiated thyroid cancer that
                  has progressed to anaplastic thyroid cancer

               -  Patients who cannot swallow oral formulations of the agent(s)

               -  Women and men of reproductive potential should agree to use an appropriate method
                  of birth control throughout their participation in this study ; appropriate
                  methods of birth control include abstinence, oral contraceptives, implantable
                  hormonal contraceptives or double barrier method (diaphragm plus condom)

               -  Efatutazone is metabolized by cytochrome P450, family 3, subfamily A, polypeptide
                  4/5 (CYP3A4/5), and inhibits CYP2C8, 2C9, 2C19, and 3A4, and is a substrate of
                  P-glycoprotein (PgP) and breast cancer resistance protein (BCRP)