Sorafenib Tosylate in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer
Condition: Hereditary Thyroid Gland Medullary Carcinoma; Locally Advanced Thyroid Gland Medullary Carcinoma; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Recurrent Thyroid Gland Medullary Carcinoma; Sporadic Thyroid Gland Medullary Carcinoma; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IV Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7
MeSH terms: Carcinoma; Neoplasms; Carcinoma, Medullary; Thyroid Neoplasms; Carcinoma, Neuroendocrine; Endocrine Gland Neoplasms; Multiple Endocrine Neoplasia; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Thyroid Diseases
Intervention: Sorafenib Tosylate
Intervention description: Given PO
Intervention MeSH terms: Sorafenib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well sorafenib tosylate works in treating patients with
      medullary thyroid cancer that has spread to other parts of the body (metastatic), spread to
      the tissue surrounding the thyroid (locally advanced), or has returned after a period of
      improvement (recurrent). Sorafenib tosylate may stop the growth of tumor cells by blocking
      some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
    

Eligibility criteria:

        Inclusion Criteria:

          -  ELIGIBILITY CRITERIA SPECIFIC FOR ARM A

          -  Histologically confirmed medullary thyroid carcinoma under the clinical setting of
             inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or
             familial medullary thyroid carcinoma (FMTC)

          -  ELIGIBILITY CRITERIA SPECIFIC FOR ARM B

          -  Histologically confirmed medullary thyroid carcinoma under the clinical setting of
             sporadic medullary thyroid carcinoma (MTC)

          -  ELIGIBILITY CRITERIA COMMON FOR ARMS A AND B

          -  Patients must have measurable disease

          -  Metastatic and/or locally advanced or locally recurrent disease

          -  Oral or intravenous (IV) bisphosphonates therapy will be allowed for patients with
             bony metastasis at the investigator's discretion; bisphosphonate usage should be
             recorded if used since these agents may have anti-farnesyl transferase activity and
             may have some therapeutic effect in combination with sorafenib

          -  Life expectancy must be >= six months

          -  Patients must have an Eastern Cooperative Oncology Group performance status 0-2

          -  Leukocytes >= 2,000/uL (10 days prior to patient enrollment)

          -  Absolute neutrophil count >= 1,000/uL (10 days prior to patient enrollment)

          -  Platelets >= 100,000/uL (10 days prior to patient enrollment)

          -  Total bilirubin =< within 2 x upper limit of normal (10 days prior to patient
             enrollment)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< within 3 x upper limit of normal (10 days prior to patient enrollment)

          -  Serum creatinine within normal institutional limits OR creatinine clearance > 30
             mL/min (by Cockcroft-Gault formula) (10 days prior to patient enrollment)

          -  The effects of sorafenib (BAY 43-9006) on the developing human fetus at the
             recommended therapeutic dose are unknown; for this reason and because kinase
             inhibitors are known to be teratogenic, 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 at
             least 30 days after completion of therapy; should a woman become pregnant or suspect
             she is pregnant while participating in this study, she should inform her treating
             physician immediately

          -  Ability to understand and the willingness to sign a written informed consent document

        Exclusion Criteria:

          -  EXCLUSION CRITERIA FOR ARM A AND B

          -  Patients who have had systemic anti-tumor therapy (such as chemotherapy, biologic
             modifiers or antiangiogenic therapy) within 4 weeks (6 weeks if nitrosourea or
             mitomycin chemotherapy) prior to study entry

          -  Patients who have had external beam radiation therapy within 1 week or if the adverse
             events associated with radiation are not resolved to grade 1 or less prior to study
             entry

          -  Prior therapy with sorafenib (BAY 43-9006), ZD 6474 or AMG-706

          -  Patients currently receiving any other tumor-specific therapy for thyroid cancer or
             investigational therapy; patients receiving adjuvant hormonal therapy for a second
             primary (such as breast cancer or prostate cancer) are allowed to participate as far
             as there are no known drug interactions

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to sorafenib (BAY 43-9006)

          -  Patients unable to swallow sorafenib tablets (e.g. any condition that impairs
             patient's ability to swallow pills)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, uncontrolled hypertension, or psychiatric illness/social situations that
             would limit compliance with study requirements

          -  Patients with any evidence of a bleeding diathesis

          -  Patients actively receiving anticoagulation with therapeutic intent; prophylactic
             anticoagulation (i.e. low dose warfarin) or venous or arterial access devices is
             allowed provided that the prothrombin time (PT), international normalized ratio (INR)
             or partial thromboplastin time (PTT) are normal

          -  Pregnant women or women who are breast-feeding are excluded from this study because
             sorafenib (BAY 43-9006) is an investigational agent and teratogenicity has not been
             evaluated yet; because there is an unknown but potential risk for adverse events in
             nursing infants secondary to treatment of the mother with sorafenib (BAY 43-9006),
             breastfeeding should be discontinued if the mother is treated with sorafenib (BAY
             43-9006)

          -  Human immunodeficiency virus (HIV)-positive patients receiving combination
             anti-retroviral therapy because of possible pharmacokinetic interactions with
             sorafenib (BAY 43-9006); patients with immune deficiency are at increased risk of
             lethal infections when treated with marrow-suppressive therapy

          -  Patients taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin,
             carbamazepine, or phenobarbital), rifampin or St. John's wort due to potential drug
             interactions with sorafenib