Intensity-Modulated Radiation Therapy and Paclitaxel With or Without Pazopanib Hydrochloride in Treating Patients With Anaplastic Thyroid Cancer
Condition: Thyroid Gland Anaplastic Carcinoma
MeSH terms: Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Carcinoma; Thyroid Diseases
Intervention: Intensity-Modulated Radiation Therapy; Paclitaxel; Pazopanib Hydrochloride; Placebo Administration
Intervention description: Undergo IMRT; Given IV; Given PO; Given PO
Intervention MeSH terms: Paclitaxel; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 123.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies the side effects and how well intensity-modulated
      radiation therapy (IMRT) and paclitaxel with or without pazopanib hydrochloride works in
      treating patients with anaplastic thyroid cancer. Specialized radiation therapy that delivers
      a high dose of radiation directly to the tumor may kill more tumor cells and cause less
      damage to normal tissue. Drugs used in chemotherapy, such as 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. Pazopanib hydrochloride may stop the growth of
      tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known
      whether radiation therapy and paclitaxel are more effective when given with pazopanib
      hydrochloride in treating thyroid cancer.
    

Eligibility criteria:

        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)

               -  Note: Tissue collection for central review is mandatory, but central review is
                  not required for eligibility; due to the aggressiveness of this disease,
                  treatment will be started prior to central review

          -  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

          -  The following minimum diagnostic workup is required:

               -  History/physical examination within 2 weeks prior to registration

               -  Imaging of neck and brain (computed tomography [CT] scan or magnetic resonance
                  imaging [MRI]) and chest/abdominal imaging (chest x-ray or chest CT scan, or full
                  body positron emission tomography [PET]/CT are acceptable) within 4 weeks prior
                  to registration

               -  Note: The CT scan of the neck must be done with contrast or if an MRI is done,
                  with gadolinium; therefore, the CT portion of a full body PET/CT has to be a high
                  resolution CT to be acceptable for eligibility

               -  Abdominal imaging must cover the liver and adrenal glands; therefore, separate
                  imaging is not required if these areas are covered by a chest CT scan

               -  Electrocardiogram within 10 days prior to registration

          -  Zubrod performance status 0-2

          -  Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 10 days prior to
             registration on study)

          -  Platelets >= 100,000 cells/mm^3 (within 10 days prior to registration on study)

          -  Hemoglobin (Hgb) >= 9.0 g/dl (within 10 days prior to registration on study) (Note:
             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's syndrome and elevations of indirect bilirubin) (within 10 days prior to
             registration)

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x
             institutional ULN (within 10 days prior to registration); Note: patients who have both
             bilirubin > ULN and AST/ALT > ULN are not eligible (unless they have Gilbert's
             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 within 10 days prior to
             registration; Note: if neither criteria is met, the creatinine clearance must be > 50
             mL/min/1.73 m^2 per either the Cockcroft-Gault equation, Jeliffe method, or 12- or
             24-hour urine collection

          -  Serum electrolytes including sodium, potassium, blood urea nitrogen (BUN), creatinine,
             glucose, magnesium, phosphate, and calcium within 10 days prior to registration

          -  Documentation of the patient's history of corrected QT interval (QTc) prolongation,
             family history of prolonged QTc, and relevant cardiac disease within 10 days prior to
             registration

          -  Evaluation of the patient's medications within 10 days prior to registration with
             attempt to change any medication that affects cytochrome P450, family 3, subfamily A,
             polypeptide 4 (CYP3A4)

          -  Blood pressure =< 140/90 within 10 days of registration (must be taken and recorded by
             a health care professional); Note: 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, and the treating physician must believe that this is feasible in order to
             enroll the patient

          -  Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time
             (PTT) within 1.2 x the upper limit of normal within 10 days prior to registration
             unless the patient is receiving coumadin and has a stable INR that is in range for the
             desired level of anticoagulation

          -  Negative pregnancy test (serum or urine) within 10 days of registration in women of
             child-bearing potential

          -  Women of childbearing potential and male participants who are sexually active must
             agree to practice adequate contraception during treatment and for 6 months
             post-treatment

          -  The patient must provide study specific informed consent prior to study entry

        Exclusion Criteria:

          -  Known active invasive malignancy (except for non-melanomatous skin cancer or
             anaplastic thyroid cancer; the presence of prostate cancer confined to the prostate
             with a prostate-specific antigen [PSA] =< 1 ng/mL for more than 6 months also is
             allowed)

          -  Prior systemic chemotherapy for anaplastic thyroid cancer

               -  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

               -  Patients receiving other investigational agents

          -  Prior radiotherapy to the region of the study cancer that would result in overlap of
             radiation therapy fields

          -  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

               -  Myocardial Infarction

               -  Cardiac angioplasty or stenting

               -  Coronary artery bypass graft surgery

               -  Pulmonary embolism, untreated deep venous thrombosis (DVT), or DVT which has been
                  treated with therapeutic anticoagulation for less than 6 weeks

               -  Arterial thrombosis

               -  Symptomatic peripheral vascular disease

               -  Class III or IV heart failure as defined by the New York Heart Association (NYHA)
                  functional classification system; Note: a patient who has a history of class III
                  heart failure and is asymptomatic on treatment may be considered eligible for the
                  study

          -  Certain medications that are associated with a risk for QTc prolongation and/or
             torsades de pointes, although not prohibited, should be avoided or replaced with
             medications that do not carry these risks, if possible

          -  Patients who require heparin (other than low-molecular weight heparin)

          -  Patients with any condition that may impair the ability to absorb oral
             medications/investigational product including:

               -  Prior surgical procedures affecting absorption including, but not limited to,
                  major resection of stomach or small bowel

               -  Active peptic ulcer disease

               -  Malabsorption syndrome

          -  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's disease) or other
                  gastrointestinal conditions which increase the risk of perforation

               -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
                  abscess within 28 days prior to beginning study treatment

          -  History of hemoptysis within 30 days of registration; Note: patients who have minimal
             bleeding from the mouth, which 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

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Pregnancy or women of childbearing potential and men who are sexually active and not
             willing/able to use medically acceptable forms of contraception; this exclusion is
             necessary because the treatment involved in this study may be significantly
             teratogenic

          -  Prior allergic reaction to the study drug(s) involved in this protocol

          -  QTc prolongation defined as a QTc interval >= 480 msecs or other significant
             electrocardiogram (EKG) abnormalities are ineligible; Note: if unsure about EKG
             abnormality, the treating physician should discuss this with Drs. Sherman or Bible

          -  Known brain metastasis

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy because of the potential for pharmacokinetic interactions with pazopanib; in
             addition, these patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy; appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated

          -  Certain medications that act through the cytochrome P450 (CYP450) system are
             specifically prohibited in patients receiving pazopanib and others should be avoided
             or administered with extreme caution

               -  Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin,
                  atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir,
                  telithromycin, voriconazole may increase pazopanib concentrations and are
                  prohibited; although, in exceptional circumstances, they may be administered in
                  conjunction with lowering the dose of pazopanib by 50% of what would otherwise be
                  administered; grapefruit juice is also an inhibitor of CYP450 and should not be
                  taken with pazopanib

               -  Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib
                  concentrations, are strictly prohibited

               -  Medications that have narrow therapeutic windows and are substrates of CYP3A4,
                  cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), or cytochrome
                  P450, family 2, subfamily C, polypeptide 8 (CYP2C8) should be avoided and, if
                  necessary, administered with caution