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

This is an interventional treatment trial for Recurrent Thyroid Gland Carcinoma Read More

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