Intensity-Modulated Radiation Therapy and Paclitaxel With or Without Pazopanib Hydrochloride in Treating Patients With Anaplastic Thyroid Cancer

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven diagnosis of anaplastic thyroid cancer (a diagnosis that is noted to be "consistent with anaplastic thyroid cancer" with the presence of a thyroid mass is acceptable)
• If there was a total or partial thyroidectomy completed within 3 months of enrollment, the surgical specimen must show the area of anaplastic thyroid cancer to be at least 1 cm in greatest dimension
• No known brain metastases
• Zubrod performance status 0-2
• Absolute neutrophil count (ANC) >= 1,500 cells/mm^3
• Platelets >= 100,000 cells/mm^3
• Hemoglobin (Hgb) >= 9.0 g/dL (the use of transfusion or other intervention to achieve Hgb >= 9.0 g/dL is acceptable)
• Total bilirubin < 1.5 x institutional upper limit of normal (ULN) (except for patients with Gilbert syndrome and elevations of indirect bilirubin)
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x institutional ULN (patients who have both bilirubin > ULN and AST/ALT > ULN are not eligible unless they have Gilbert syndrome and elevations of indirect bilirubin)
• Spot urine protein to creatinine ratio (UPCR) < 1 or a 24-hour urine protein collection < 1 gm) within 10 days prior to registration
• Creatinine < 1.5 mg/dL or within normal institutional limits (if neither criteria is met, the creatinine clearance must be > 50 mL/min^2 per either the Cockcroft-Gault equation, Jeliffe method, or 12- or 24-hour urine collection)
• Documentation of the patient's history of QTc prolongation, family history of prolonged QTc, and relevant cardiac disease
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use adequate contraception during and for at least 6 months of completing study therapy

• Blood pressure < 140/90 within 10 days of registration (must be taken and recorded by a health care professional)

  • If the systolic blood pressure is > 140 and/or diastolic blood pressure is > 90 at the time of registration, the patient's blood pressure must be controlled
  • Systolic blood pressure must be < 140 and diastolic blood pressure must be < 90 on at least 2 separate measurements prior to the start of treatment
  • The treating physician must believe that this is feasible in order to enroll the patient
• No known active invasive malignancy (except for nonmelanomatous skin cancer, differentiated thyroid cancer, or the presence of prostate cancer confined to the prostate with a PSA < 1 ng/mL for more than 6 months)

• No patients with any of the following cardiovascular conditions within the past 6 months:

  • Cerebrovascular accident (CVA) or transient ischemic attack (TIA)
  • Admission for unstable angina
  • Cardiac angioplasty or stenting
  • Coronary artery bypass graft surgery
  • Pulmonary embolism, untreated deep venous thrombosis (DVT), or DVT that has been treated with therapeutic anticoagulation for less than 6 weeks
  • Arterial thrombosis
  • Symptomatic peripheral vascular disease
  • Class II-IV heart failure as defined by the New York Heart Association (NYHA) functional classification system (a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible for the study)
• Patients with an arrhythmia are excluded
• Patients with atrial fibrillation, supraventricular tachycardia, or bradycardia are eligible but these conditions must be well controlled with medication or a pacemaker

• No patients with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:

  • Any lesion, whether induced by tumor, radiation, or other conditions, that makes it difficult to swallow capsules or pills
  • Prior surgical procedures affecting absorption including, but not limited to, major resection of stomach or small bowel
  • Active peptic ulcer disease
  • Malabsorption syndrome

• No patients with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:

  • Active peptic ulcer disease
  • Known intraluminal metastatic lesions
  • Inflammatory bowel disease (e.g., ulcerative colitis, Crohn disease) or other gastrointestinal conditions that increase the risk of perforation
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days prior to beginning study treatment

• No history of hemoptysis within 30 days of registration

  • Patients who have minimal bleeding from the mouth that is clearly not related to a source in the lungs (i.e., surgery such as a non-lung biopsy) are eligible only after good hemostasis has been documented
• No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements
• No prior allergic reaction to the study drug(s) involved in this protocol
• Patients with QTc prolongation defined as a QTc interval > 480 msecs or other significant electrocardiogram (EKG) abnormalities are ineligible
• No human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
• No concurrent St. John wort

• No prior systemic chemotherapy for anaplastic thyroid cancer

  • No patients who have had chemotherapy or radiotherapy within 4 weeks of registration (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered > 4 weeks previously
• No patients receiving other investigational agents
• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields
• No patients who require heparin (other than low-molecular weight heparin)
• Strong inducers of CYP3A4, such as rifampin, are strictly prohibited
• Strong inhibitors of CYP3A4, including grapefruit juice, are prohibited