Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

Inclusion Criteria:

* Histopathologically confirmed differentiated thyroid carcinoma of follicular cell origin, including any of the following histologies and their respective variants:

  * Papillary
  * Follicular
  * Hürthle cell
* Must have surgically inoperable and/or recurrent or metastatic disease
* At least one fludeoxyglucose F 18 (FDG)-PET-avid lesion, defined as any focus of increased FDG uptake \> normal mediastinal activity with standard uptake variable (SUV) maximum levels ≥ 3, as documented by baseline PET scan
* Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
* Progressive disease, defined by ≥ 1 of the following occurring during or after prior treatment (e.g., radioactive isotope \[RAI\] treatment):

  * Presence of new or progressive lesions on CT scan or MRI
  * New lesions on bone scan or PET scan
  * Rising thyroglobulin level documented by a minimum of 3 consecutive rises, with an interval of \> 1 week between each determination
* No known history of brain metastasis
* ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
* ANC ≥ 1,500/mcL
* Platelet count ≥ 75,000/mcL
* WBC ≥ 3,000/mcL
* Total bilirubin ≤ 1.5 times upper limit of normal(ULN)
* AST and ALT ≤ 2.5 times ULN (≤ 5 times ULN for liver metastases)
* Creatinine ≤ 1.5 times ULNOR creatinine clearance ≥ 60 mL/min
* INR ≤ 1.2 (≤ 1.5 times ULN if on prophylactic-dose anticoagulation)
* Urine protein: creatinine ratio \< 1 OR 24-hour urine protein \< 500 mg
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception during and for ≥ 6 months after completion of study therapy
* Documentation of systolic blood pressure ≤150 mm Hg and diastolic blood pressure ≤100 mm Hg
* No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to other agents used in the study
* No serious or non-healing wound, ulcer, or bone fracture
* No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess in the past 28 days
* No significant traumatic injury within the past 28 days
* No clinically significant cardiovascular disease, defined as any of the following:

  * Cerebrovascular accident within the past 6 months
  * Myocardial infarction within the past 6 months
  * Coronary artery bypass grafting or unstable angina within the past 6 months
  * NYHA grade III-IV congestive heart failure
  * Canadian Cardiovascular Class grade III or greater angina within the past 6 months
  * Clinically significant peripheral vascular disease within the past 6 months
  * Pulmonary embolism, deep-vein thrombosis, or other thromboembolic event within the past 6 months
  * Uncontrolled coronary artery disease, angina, congestive heart failure, or ventricular arrhythmia requiring acute medical management
  * Myocardial infarction, cerebrovascular accident, or transient ischemic attack within the past 6 months
* No evidence of bleeding diathesis or coagulopathy within the past 12 months
* No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness or social situation that would limit study compliance
* No known HIV positivity
* See Disease Characteristics
* Recovered from prior therapy
* No prior VEGF-targeted antibody therapy (e.g., bevacizumab or aflibercept)
* More than 4 weeks since prior systemic therapy or radiotherapy
* More than 7 days since prior core biopsy
* Up to 1 prior targeted biologic agent (e.g., small-molecule tyrosine kinase inhibitor or histone deacetylase inhibitor) allowed provided treatment was stopped ≥ 4 weeks prior to initiation of therapy on this study
* Up to 1 prior cytotoxic chemotherapy (e.g., doxorubicin hydrochloride) allowed provided treatment was stopped ≥ 4 weeks prior to initiation of therapy on this study
* Prior systemic chemotherapy administered as part of initial definitive treatment (e.g., as a radiation sensitizer or as initial adjuvant therapy) allowed provided treatment was stopped ≥ 3 months prior to initiation of therapy on this study and does not count in the determination of prior targeted or cytotoxic therapy
* At least 2 weeks since prior cyclooxygenase-2 (COX-2) inhibitors, cis-retinoic acid, or complementary medications if given with anti-cancer intent

  * Medications given for a specific clinical indication (e.g., daily aspirin status post myocardial infarction or COX-2 inhibitors at standard anti-inflammatory/pain doses) may be continued based on the clinical judgment of the involved investigator
* Prior RAI therapy allowed provided it was stopped \> 3 months prior to initiation of therapy on this protocol and evidence of progression (as defined above) has been documented in the interim

  * A diagnostic study using \< 10 mCi of RAI is not considered RAI therapy
* Prior external-beam radiotherapy to index lesions allowed provided there has been documented progression by RECIST criteria and at least 4 weeks have elapsed

  * At least 4 weeks since prior external-beam radiation therapy to non-index lesions
* At least 4 weeks since prior surgery
* Concurrent therapeutic-dose anticoagulants (e.g., warfarin) with PT INR \> 1.5 allowed provided that both of the following criteria are met:

  * In-range INR appropriate to the treatment indication (e.g., between 2 and 3 for atrial fibrillation) AND on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
  * No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
* Patients receiving concurrent antihypertensive agents must have documentation of the date of the last change in dosage
* No other concurrent investigational agents
* No major surgical procedure or open biopsy within the past 28 days
* No anticipation of need for major surgical procedures during the course of the study