Phase II Trial of Sorafenib (Nexavar) in Patients With Advanced Thyroid Cancer
Condition: Metastatic Differentiated Thyroid Cancer; Metastatic Poorly Differentiated Thyroid Cancer; Metastatic Anaplastic Thyroid Cancer; Metastatic Medullary Thyroid Cancer
MeSH terms: Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Thyroid Diseases
Intervention: sorafenib
Intervention description: 400mg PO BID daily
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 59.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Thyroid Cancer; Anaplastic; Medullary; sorafenib

Summary:

      The goal of this study is to determine the activity of sorafenib in patients with advanced
      (metastatic or recurrent) thyroid cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically confirmed thyroid cancer that is metastatic or
             unresectable and for which standard curative or palliative measures do not exist or
             are no longer effective.

          -  Patients may have received multiple treatments of radioactive iodine, one prior
             biologic treatment, and at least half of the patients will have had no prior
             chemotherapy for metastatic disease. At least 3 weeks must have elapsed since prior
             treatment.

          -  Measurable disease defined as at least one malignant lesion that can be accurately and
             serially measured in at least one dimension (longest diameter to be recorded), using a
             caliper (diameter > 10 mm) for superficial cutaneous disease, or using
             contrast-enhanced CT or spiral CT (diameter > 20 mm) for visceral or nodal/soft tissue
             disease.

          -  ECOG performance status < 2 (Appendix 1).

          -  Life expectancy greater than 3 months.

          -  Adequate organ function that has been determined within 7 days prior to enrollment,
             defined as:Leucocyte count > 3,000/uL; Absolute neutrophil count (ANC) > 1,500/mm3,
             platelets > 100,000/mm3, and hemoglobin > 9 g/dl; Serum creatinine < 1.5 times ULN, or
             24-hour creatinine clearance > 75 cc/min. (Note: creatinine clearance need not be
             determined if the baseline serum creatinine is within normal limits); Serum bilirubin
             < 1.5 times ULN; serum glutamyloxaloacetic transaminase (SGOT) < 2.5 ULN; alkaline
             phosphatase < 2.5 times ULN; PT-INR/PTT < 1.5 x upper limit of normal.

          -  Intellectual, emotional, and physical ability to comply with oral medication.

          -  Ability to understand and the willingness to sign a written informed consent

          -  Patients with disease accessible for biopsy will be preferentially selected for
             participation in the study. Accessible disease includes lymph node metastases.

          -  Female patients of child-bearing potential must have a negative pregnancy test within
             14 days before initiation of study drug dosing. Post-menopausal women must be
             amenorrheic for at least 12 months to be considered non-child-bearing potential. Male
             and female patients of reproductive potential must agree to use adequate contraception
             (i.e. hormonal or barrier method of birth control). throughout the study and for 3
             months after the study.

        Exclusion Criteria:

          -  Significant medical disease including: uncontrolled congestive heart failure; active
             symptoms of coronary artery disease, uncontrolled seizure disorder; active infection;
             uncontrolled diabetes mellitus; requirement for chronic corticosteroid treatment;
             requirement for concurrent immunosuppressive drug(s); active autoimmune disease.

          -  Organ allografts.

          -  Known HIV-infection (HIV testing is not required for participation).

          -  Pregnancy or lactation. Women of childbearing potential and sexually active males must
             be advised to take precautions to prevent pregnancy during treatment

          -  History of second cancer (except adequately treated basal cell or squamous cell skin
             cancer, in situ cervical cancer, or other cancer for which the patient has been
             disease-free for five or more years).

          -  Use of any experimental therapy within 3 weeks prior to baseline evaluations done
             prior to enrollment.

          -  Patients with carcinomatous meningitis are excluded from the study.

          -  Excluded therapies and medications, previous and concomitant:Anticancer chemotherapy
             or immunotherapy during the study or within 4 weeks prior to the first dose of the
             study drug; Radiotherapy for the treatment of a symptomatic (e.g. bone metastasis) as
             clinically indicated is allowed as long as it is not evidence of progressive disease
             (see 4.5.2); -Biological response modifiers, such as G-CSF, within 3 week prior to
             study entry. (G-CSF and other hematopoietic growth factors may be used in the
             management of acute toxicity such as febrile neutropenia when clinically indicated or
             at the discretion of the investigator; however they may not be substituted for a
             required dose reduction); Patients taking chronic erythropoietin are permitted
             provided no dose adjustment is undertaken within 2 months prior to the study or during
             the study; Investigational drug therapy outside of this trial during or within 4 weeks
             prior the screening assessment; Use of ketoconazole, itraconazole, and ritonavir; Use
             of carbamazepine, phenytoin, phenobarbital; Previous exposure to a Ras pathway
             inhibitor (including herceptin, EGFr inhibitors, farnesyl transferase inhibitors or
             MEK inhibitors); Use of grapefruit juice products; Use of cyclosporin;

          -  Pregnant or breast feeding.