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

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ClinicalTrials.gov Identifier: NCT00729157
Recruitment Status : Completed
First Posted : August 7, 2008
Results First Posted : March 15, 2017
Last Update Posted : March 15, 2017
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions 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
Interventions Radiation: Fludeoxyglucose F-18
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
Procedure: Positron Emission Tomography
Biological: Ziv-Aflibercept
Enrollment 41

Recruitment Details  
Pre-assignment Details  
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description Patients receive aflibercept 4mg/kg 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.
Period Title: Overall Study
Started 41
Completed 40
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description Patients receive aflibercept 4mg/kg 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.
Overall Number of Baseline Participants 41
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants
<=18 years
0
   0.0%
Between 18 and 65 years
20
  48.8%
>=65 years
21
  51.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants
Female
22
  53.7%
Male
19
  46.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 41 participants
41
1.Primary Outcome
Title Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
Hide Description Progression-free survival to determine the 6-month progression-free-survival (PFS) rate
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description:
Patients receive aflibercept 4mg/kg 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.
Overall Number of Participants Analyzed 18
Median (95% Confidence Interval)
Unit of Measure: months
5.4
(1.6 to 30.8)
2.Primary Outcome
Title Radiographic Response Rate of Aflibercept in Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Hide Description 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
Time Frame After 8 weeks of study therapy
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description:
Patients receive aflibercept 4mg/kg 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.
Overall Number of Participants Analyzed 40
Measure Type: Number
Unit of Measure: participants
Progression of Disease 7
Stable Disease 33
3.Secondary Outcome
Title The Safety and Toxicity Profile of IV VEGF Trap in Patients With Recurrent and/or Metastatic TC-FCO
Hide Description The number of participants, with recurrent and/or metastatic TC-FCO, who experienced adverse events. Please see the adverse event table for the specifics for this protocol.
Time Frame From the beginning of treatment through 30 days until participant comes off study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description:
Patients receive aflibercept 4mg/kg 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.
Overall Number of Participants Analyzed 41
Measure Type: Number
Unit of Measure: participants
36
4.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame 8 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description:
Patients receive aflibercept 4mg/kg 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.
Overall Number of Participants Analyzed 8
Median (95% Confidence Interval)
Unit of Measure: percent of SUVm change
.64
(-6.91 to 12.67)
5.Secondary Outcome
Title Effect of Thyroglobulin Concentration on Progression-free Survival
Hide Description The change is serum thyroglobulin was measured by the percent change between the baseline value and the lowest value obtained while on treatment.
Time Frame 6 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description:
Patients receive aflibercept 4mg/kg 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.
Overall Number of Participants Analyzed 36
Median (Full Range)
Unit of Measure: percent change serum thyroglobulin
0.4
(0 to 90)
6.Other Pre-specified Outcome
Title To Determine if Pre-treatment Serum VEGF Concentration Correlates With Clinical Outcomes After IV VEGF Trap Therapy in Patients With Recurrent and/or Metastatic D-TC-FCO.
Hide Description This part is currently under data analysis, therefore, this outcome measure has not been calculatedThis part is currently under data analysis, therefore, this outcome measure has not been calculated.
Time Frame Baseline-6 months post treatment
Outcome Measure Data Not Reported
7.Other Pre-specified Outcome
Title To Determine if Changes in Thyroglobulin Concentration After Four Cycles (Approximately 8 Weeks) of IV VEGF-Trap Therapy Correlate With Radiographic Response After Four Cycles (Approximately 8 Weeks)
Hide Description This part is currently under data analysis, therefore, this outcome measure has not been calculated
Time Frame 8 weeks
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Hide Arm/Group Description Patients receive aflibercept 4mg/kg 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.
All-Cause Mortality
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Affected / at Risk (%) # Events
Total   24/41 (58.54%)    
Blood and lymphatic system disorders   
Anemia  1  1/41 (2.44%)  1
Cardiac disorders   
Cardiac disorder  1  1/41 (2.44%)  1
Myocardial infarction  1  2/41 (4.88%)  2
Endocrine disorders   
Hyperthyroidism  1  1/41 (2.44%)  1
Gastrointestinal disorders   
Diarrhea  1  1/41 (2.44%)  1
Dysphagia  1  2/41 (4.88%)  3
Duodenal hemorrhage  1  1/41 (2.44%)  1
Nausea  1  1/41 (2.44%)  1
Abdominal pain  1  1/41 (2.44%)  1
Anal pain  1  1/41 (2.44%)  1
General disorders   
Death not assoc w CTCAE term-Disease prog NOS  1  2/41 (4.88%)  2
Edema: limb  1  1/41 (2.44%)  1
Fatigue  1  2/41 (4.88%)  2
Non-cardiac Chest pain  1  2/41 (4.88%)  2
Infections and infestations   
Urinary tract infection  1  1/41 (2.44%)  1
Investigations   
Lymphocyte count decrease  1  5/41 (12.20%)  5
Platelet count decrease  1  1/41 (2.44%)  1
Metabolism and nutrition disorders   
Hypocalcemia  2  2/41 (4.88%)  2
Hypermagnesemia  1  1/41 (2.44%)  1
Musculoskeletal and connective tissue disorders   
Joint disorder  1  4/41 (9.76%)  4
Muscle weakness upper limb  1  4/41 (9.76%)  4
Back pain  1  1/41 (2.44%)  1
Buttock pain  1  1/41 (2.44%)  1
Pain in extremity  1  1/41 (2.44%)  1
Neck pain  1  2/41 (4.88%)  2
Nervous system disorders   
Cerebrovascular ischemia  1  1/41 (2.44%)  1
Neurological disorder  1  1/41 (2.44%)  1
Peripheral sensory neuropathy  1  1/41 (2.44%)  2
Headache  1  2/41 (4.88%)  2
Syncope  1  1/41 (2.44%)  1
Psychiatric disorders   
Confusion  1  2/41 (4.88%)  2
Renal and urinary disorders   
Proteinuria  1  5/41 (12.20%)  5
Renal failure  1  1/41 (2.44%)  1
Respiratory, thoracic and mediastinal disorders   
Dyspnea  1  3/41 (7.32%)  4
Pneumonia  1  1/41 (2.44%)  1
Pleural effusion  1  2/41 (4.88%)  2
Vascular disorders   
Hematoma  1  1/41 (2.44%)  1
Hypertension  1  3/41 (7.32%)  3
Hypotension  1  2/41 (4.88%)  2
Thrombosis  1  1/41 (2.44%)  1
Thrombotic microangiopathy  1  1/41 (2.44%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
2
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Affected / at Risk (%) # Events
Total   36/41 (87.80%)    
Blood and lymphatic system disorders   
Anemia  1  2/41 (4.88%)  4
Gastrointestinal disorders   
Dysphagia  1  3/41 (7.32%)  3
Nausea  1  2/41 (4.88%)  2
Vomiting  1  3/41 (7.32%)  3
General disorders   
Fatigue  1  8/41 (19.51%)  13
Investigations   
Blood bilirubin increased  1  4/41 (9.76%)  11
INR increased  1  2/41 (4.88%)  27
Lymphocyte count decreased  1  5/41 (12.20%)  15
White blood cell decreased  1  2/41 (4.88%)  16
Metabolism and nutrition disorders   
Anorexia  1  4/41 (9.76%)  4
Hyperglycemia  1  14/41 (34.15%)  70
Hyperkalemia  1  3/41 (7.32%)  5
Hypoalbuminemia  1  2/41 (4.88%)  6
Hypocalcemia  1  11/41 (26.83%)  37
Hypophosphatemia  1  3/41 (7.32%)  4
Musculoskeletal and connective tissue disorders   
Arthralgia  1  7/41 (17.07%)  11
Bone pain  1  2/41 (4.88%)  2
Nervous system disorders   
Headache  1  6/41 (14.63%)  8
Peripheral sensory neuropathy  1  2/41 (4.88%)  2
Renal and urinary disorders   
Proteinuria  1  9/41 (21.95%)  20
Respiratory, thoracic and mediastinal disorders   
Cough  1  5/41 (12.20%)  6
Skin and subcutaneous tissue disorders   
Rash acneiform  1  2/41 (4.88%)  2
Vascular disorders   
Hypertension  1  8/41 (19.51%)  9
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. David Pfister
Organization: Memorial Sloan Kettering Cancer Center
Phone: 646-888-4237
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00729157     History of Changes
Other Study ID Numbers: NCI-2009-00178
NCI-2009-00178 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MSKCC-08066
CDR0000608163
08-066 ( Other Identifier: Memorial Sloan-Kettering Cancer Center )
7508 ( Other Identifier: CTEP )
N01CM62206 ( U.S. NIH Grant/Contract )
P30CA008748 ( U.S. NIH Grant/Contract )
First Submitted: August 6, 2008
First Posted: August 7, 2008
Results First Submitted: February 26, 2016
Results First Posted: March 15, 2017
Last Update Posted: March 15, 2017