Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Condition: Recurrent Thyroid Gland Carcinoma; Stage III Thyroid Gland Follicular Carcinoma; Stage III Thyroid Gland Papillary Carcinoma; Stage IV Thyroid Gland Follicular Carcinoma; Stage IV Thyroid Gland Papillary Carcinoma
MeSH terms: Carcinoma; Thyroid Neoplasms; Carcinoma, Papillary; Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Thyroid Diseases; Recurrence
Intervention: Fludeoxyglucose F-18; Laboratory Biomarker Analysis; Pharmacological Study; Positron Emission Tomography; Ziv-Aflibercept
Intervention description: Correlative studies; Correlative studies; Correlative studies; Correlative studies; Given IV
Intervention MeSH terms: Deoxyglucose; Aflibercept; Endothelial Growth Factors; Fluorodeoxyglucose F18
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how well aflibercept works in treating patients with
      recurrent and/or metastatic thyroid cancer that has not responded to radioactive iodine
      therapy. Aflibercept may stop the growth of tumor cells by blocking blood flow to the tumor
      and by carrying tumor-killing substances directly to thyroid cancer cells.
    

Eligibility criteria:

        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