Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

Inclusion Criteria:

• Histologically or cytologically confirmed thyroid cancer that is now advanced or metastatic disease

  • One of the following subtypes:

    • Differentiated thyroid cancer
    • Absence of sensitivity to therapeutic radioiodine
    • Medullary thyroid cancer
    • Anaplastic thyroid cancer
• Patients with confirmed differentiated thyroid cancer (DTC) must be thyroglobulin antibody negative to be enrolled in the expanded/additional DTC cohort
• Zero, one or two prior therapeutic regimens (this includes cytotoxic plus non-cytotoxic therapeutic regimens)
• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral computed tomography (CT) scan

• Objective evidence of tumor progression within the past 6 months, as assessed by the following:

  • Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g., CT scan); in cases of uncertainty of tumor progression, the Principal Investigator of the study will be available to assist in decisions
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%
• Life expectancy > 3 months
• Leukocytes ≥ 3,000/mcL
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (direct bilirubin ≤ 1.5 times ULN if patient has Gilbert syndrome)
• Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 times ULN
• Creatinine ≤ 1.5 times ULN

• Proteinuria ≤ 1+ on urinalysis

  • No proteinuria > 1+ (< 30 mg/dL) on two consecutive dipstick or other urine assessments taken at least 1 week apart
• International normalized ratio (INR) ≤ 1.2 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception prior to and during study therapy

• Systolic blood pressure (BP) < 140 mm Hg and diastolic BP < 90 mm Hg

  • Initiation or adjustment of BP medication is permitted prior to registration provided the average of three BP readings at a visit prior to registration is < 140/90 mm Hg
• No sensitivity to therapeutic radioiodine (differentiated only)
• Able to understand and willing to sign a written informed consent document
• Willing to comply with the requirements of the study
• Willing to donate blood for correlative marker studies (only applicable to sites within the United States)
• No admission for unstable angina, cardiac angioplasty, or stenting within the past 12 weeks
• At least 4 weeks since prior radiotherapy
• At least 4 weeks since prior major surgery
• No prior surgical procedure affecting absorption
• No requirement for IV alimentation
• No prior radiotherapy to ≥ 25% of bone marrow

• No concurrent octreotide

  • Concurrent octreotide allowed provided tumor progression on this drug has been demonstrated
• No other concurrent investigational agents
• No cytochrome (CYP) interactive medications prior to, during, and for at least 1-2 weeks after discontinuation from the study
• No concurrent antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients
• No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride
• No concurrent investigational or commercial agents or therapies other than those used for this study with the intent to treat the patient's malignancy

• No concurrent therapeutic warfarin

  • Low molecular weigh the paring and prophylactic low-dose warfarin allowed

• No more than 2 total prior cytotoxic or noncytotoxic therapeutic regimens

  • Up to two total prior noncytotoxic or cytotoxic therapeutic regimens are allowed provided therapy ceased > 21 days prior to registration
• No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes

Exclusion Criteria:

• Thyroid lymphomas, sarcomas, or metastatic disease from other sites of origin to thyroid
• Disease that is measurable by physical examination only
• Known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g., corticosteroids)
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib hydrochloride or other agents used in the study
• QTc prolongation (defined as a QTc interval ≥ 4800 msecs) or other significant electrocardiogram (ECG) abnormalities (e.g., frequent ventricular ectopy or evidence of ongoing myocardial ischemia); NOTE: the Principal Investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon ECG changes

• Any condition that impairs the ability to swallow and retain pazopanib hydrochloride, including any of the following:

  • Gastrointestinal tract disease resulting in an inability to take oral medication
  • Active peptic ulcer disease

• Any of the following conditions:

  • Serious or nonhealing wound, ulcer, or bone fracture
  • History of abdominal fistula
  • Gastrointestinal perforation
  • Active diverticulitis
  • Intra-abdominal abscess or gastrointestinal tract bleeding within the past 28 days prior to registration
  • History of cerebrovascular accident (CVA) within the past 6 months
  • History of myocardial infarction, cardiac arrhythmia within the past 12 weeks
  • History of venous thrombosis within the past 12 weeks
  • NYHA class III or IV heart failure
  • History of bleeding disorder including hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding
  • Poorly controlled depression or anxiety disorder, or recent (≤ 6 months)suicidal ideation
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonably be expected to limit compliance with study requirements