A Phase II Study of Single Agent Intravenous (IV) VEGF Trap in Patients With Poor Prognostic Recurrent and/or Metastatic Thyroid Cancer After RAI Therapy
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES:
I. To determine the radiographic response rate (by RECIST criteria) of IV VEGF Trap after four cycles (approximately 8 weeks) of therapy, as well as the 6-month progression-free-survival (PFS) rate (as part of a composite primary outcome measure), in patients with recurrent and/or metastatic differentiated thyroid carcinoma of follicular cell origin (D-TC-FCO; comprising papillary, follicular, Hurthle cell, and respective variants) not amenable to RAI or curative surgery.
SECONDARY OBJECTIVES:
I. To determine the safety and toxicity profile of IV VEGF Trap in patients with recurrent and/or metastatic TC-FCO. Please see the adverse event table for the specifics for this protocol.
II. To determine the biologic effect of IV VEGF Trap on FDG avidity after four cycles (approximately 8 weeks) of therapy through pre- and post-treatment FDG-PET scans in patients with recurrent and/or metastatic D-TC-FCO.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- 另有 15 项未显示
排除标准
- 未提供
研究组 & 干预措施
Treatment (ziv-aflibercept and fludeoxyglucose F 18)
Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients experiencing clear clinical benefit with aflibercept may continue treatment beyond 12 months, at the discretion of the study sponsor. Patients undergo FDG-PET scans at baseline and after 8 weeks of study therapy to evaluate changes in FDG avidity on FDG-PET scan. Blood samples are obtained at baseline and periodically during study for laboratory correlative studies. Samples are examined for pretreatment serum VEGF concentration, thyroglobulin levels (when elevated), serum pharmacokinetics of aflibercept by ELISA, and anti-aflibercept antibodies.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (ziv-aflibercept and fludeoxyglucose F 18)
Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients experiencing clear clinical benefit with aflibercept may continue treatment beyond 12 months, at the discretion of the study sponsor. Patients undergo FDG-PET scans at baseline and after 8 weeks of study therapy to evaluate changes in FDG avidity on FDG-PET scan. Blood samples are obtained at baseline and periodically during study for laboratory correlative studies. Samples are examined for pretreatment serum VEGF concentration, thyroglobulin levels (when elevated), serum pharmacokinetics of aflibercept by ELISA, and anti-aflibercept antibodies.
干预措施: Pharmacological Study (Other)
Treatment (ziv-aflibercept and fludeoxyglucose F 18)
Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients experiencing clear clinical benefit with aflibercept may continue treatment beyond 12 months, at the discretion of the study sponsor. Patients undergo FDG-PET scans at baseline and after 8 weeks of study therapy to evaluate changes in FDG avidity on FDG-PET scan. Blood samples are obtained at baseline and periodically during study for laboratory correlative studies. Samples are examined for pretreatment serum VEGF concentration, thyroglobulin levels (when elevated), serum pharmacokinetics of aflibercept by ELISA, and anti-aflibercept antibodies.
干预措施: Positron Emission Tomography (Procedure)
Treatment (ziv-aflibercept and fludeoxyglucose F 18)
Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients experiencing clear clinical benefit with aflibercept may continue treatment beyond 12 months, at the discretion of the study sponsor. Patients undergo FDG-PET scans at baseline and after 8 weeks of study therapy to evaluate changes in FDG avidity on FDG-PET scan. Blood samples are obtained at baseline and periodically during study for laboratory correlative studies. Samples are examined for pretreatment serum VEGF concentration, thyroglobulin levels (when elevated), serum pharmacokinetics of aflibercept by ELISA, and anti-aflibercept antibodies.
干预措施: Ziv-Aflibercept (Biological)
Treatment (ziv-aflibercept and fludeoxyglucose F 18)
Patients receive aflibercept IV over 1 hour on day 1. Treatment repeats every 14 days for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients experiencing clear clinical benefit with aflibercept may continue treatment beyond 12 months, at the discretion of the study sponsor. Patients undergo FDG-PET scans at baseline and after 8 weeks of study therapy to evaluate changes in FDG avidity on FDG-PET scan. Blood samples are obtained at baseline and periodically during study for laboratory correlative studies. Samples are examined for pretreatment serum VEGF concentration, thyroglobulin levels (when elevated), serum pharmacokinetics of aflibercept by ELISA, and anti-aflibercept antibodies.
干预措施: Fludeoxyglucose F-18 (Radiation)
结局指标
主要结局
Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
时间窗: 6 months
Progression-free survival to determine the 6-month progression-free-survival (PFS) rate
Radiographic Response Rate of Aflibercept in Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
时间窗: After 8 weeks of study therapy
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions \& assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + P RMeasurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ≥ 20 mm with conventional techniques (CT, MRI, x-ray) or as ≥ 10 mm with spiral CT scan. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). All other lesions (or sites of disease), including small lesions (longest diameter \< 20 mm with conventional techniques or \< 10 mm using spiral CT scan), are considered non-measurable disease. Bone lesions, leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonis, inflammatory breast disease, abdominal masses (not followed by CT or MRI), \& cystic
次要结局
- Effect of Thyroglobulin Concentration on Progression-free Survival(6 months)
- To Determine the Biologic Effect of IV VEGF Trap on FDG Avidity After Four Cycles (Approximately 8 Weeks) of Therapy Through Pre- and Post-treatment FDG-PET Scans in Patients With Recurrent and/or Metastatic D-TC-FCO.(8 weeks)
- The Safety and Toxicity Profile of IV VEGF Trap in Patients With Recurrent and/or Metastatic TC-FCO(From the beginning of treatment through 30 days until participant comes off study)