Trial Outcomes & Findings for Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy (NCT NCT00729157)
NCT ID: NCT00729157
Last Updated: 2017-03-15
Results Overview
Progression-free survival to determine the 6-month progression-free-survival (PFS) rate
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
41 participants
Primary outcome timeframe
6 months
Results posted on
2017-03-15
Participant Flow
Participant milestones
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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 Study
STARTED
|
41
|
|
Overall Study
COMPLETED
|
40
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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.
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|---|---|
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Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Baseline characteristics by cohort
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=41 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
21 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
United States
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41 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 6 monthsProgression-free survival to determine the 6-month progression-free-survival (PFS) rate
Outcome measures
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=18 Participants
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.
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|---|---|
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Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
|
5.4 months
Interval 1.6 to 30.8
|
PRIMARY outcome
Timeframe: After 8 weeks of study therapyPer 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
Outcome measures
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=40 Participants
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.
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|---|---|
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Radiographic Response Rate of Aflibercept in Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Progression of Disease
|
7 participants
|
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Radiographic Response Rate of Aflibercept in Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy
Stable Disease
|
33 participants
|
SECONDARY outcome
Timeframe: From the beginning of treatment through 30 days until participant comes off studyThe 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.
Outcome measures
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=41 Participants
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.
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|---|---|
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The Safety and Toxicity Profile of IV VEGF Trap in Patients With Recurrent and/or Metastatic TC-FCO
|
36 participants
|
SECONDARY outcome
Timeframe: 8 weeksTo 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.
Outcome measures
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=8 Participants
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.
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|---|---|
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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.
|
.64 percent of SUVm change
Interval -6.91 to 12.67
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SECONDARY outcome
Timeframe: 6 monthsThe change is serum thyroglobulin was measured by the percent change between the baseline value and the lowest value obtained while on treatment.
Outcome measures
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=36 Participants
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.
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|---|---|
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Effect of Thyroglobulin Concentration on Progression-free Survival
|
0.4 percent change serum thyroglobulin
Interval 0.0 to 90.0
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OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline-6 months post treatmentThis 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.
Outcome measures
Outcome data not reported
OTHER_PRE_SPECIFIED outcome
Timeframe: 8 weeksThis part is currently under data analysis, therefore, this outcome measure has not been calculated
Outcome measures
Outcome data not reported
Adverse Events
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
Serious events: 24 serious events
Other events: 36 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=41 participants at risk
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.
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|---|---|
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Nervous system disorders
Cerebrovascular ischemia
|
2.4%
1/41 • Number of events 1
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
4.9%
2/41 • Number of events 2
|
|
Cardiac disorders
Cardiac disorder
|
2.4%
1/41 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
4.9%
2/41 • Number of events 2
|
|
Psychiatric disorders
Confusion
|
4.9%
2/41 • Number of events 2
|
|
General disorders
Death not assoc w CTCAE term-Disease prog NOS
|
4.9%
2/41 • Number of events 2
|
|
Gastrointestinal disorders
Diarrhea
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Dysphagia
|
4.9%
2/41 • Number of events 3
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.3%
3/41 • Number of events 4
|
|
General disorders
Edema: limb
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Fatigue
|
4.9%
2/41 • Number of events 2
|
|
Vascular disorders
Hematoma
|
2.4%
1/41 • Number of events 1
|
|
Blood and lymphatic system disorders
Anemia
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Duodenal hemorrhage
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
Hypertension
|
7.3%
3/41 • Number of events 3
|
|
Vascular disorders
Hypotension
|
4.9%
2/41 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonia
|
2.4%
1/41 • Number of events 1
|
|
Infections and infestations
Urinary tract infection
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Joint disorder
|
9.8%
4/41 • Number of events 4
|
|
Investigations
Lymphocyte count decrease
|
12.2%
5/41 • Number of events 5
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Muscle weakness upper limb
|
9.8%
4/41 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Neurological disorder
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
2.4%
1/41 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal pain
|
2.4%
1/41 • Number of events 1
|
|
Gastrointestinal disorders
Anal pain
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
2.4%
1/41 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Buttock pain
|
2.4%
1/41 • Number of events 1
|
|
General disorders
Non-cardiac Chest pain
|
4.9%
2/41 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Headache
|
4.9%
2/41 • Number of events 2
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
4.9%
2/41 • Number of events 2
|
|
Investigations
Platelet count decrease
|
2.4%
1/41 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
4.9%
2/41 • Number of events 2
|
|
Renal and urinary disorders
Proteinuria
|
12.2%
5/41 • Number of events 5
|
|
Renal and urinary disorders
Renal failure
|
2.4%
1/41 • Number of events 1
|
|
Nervous system disorders
Syncope
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
Thrombosis
|
2.4%
1/41 • Number of events 1
|
|
Vascular disorders
Thrombotic microangiopathy
|
2.4%
1/41 • Number of events 1
|
|
Endocrine disorders
Hyperthyroidism
|
2.4%
1/41 • Number of events 1
|
Other adverse events
| Measure |
Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
n=41 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
4.9%
2/41 • Number of events 4
|
|
Metabolism and nutrition disorders
Anorexia
|
9.8%
4/41 • Number of events 4
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.1%
7/41 • Number of events 11
|
|
Investigations
Blood bilirubin increased
|
9.8%
4/41 • Number of events 11
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.9%
2/41 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.2%
5/41 • Number of events 6
|
|
Gastrointestinal disorders
Dysphagia
|
7.3%
3/41 • Number of events 3
|
|
General disorders
Fatigue
|
19.5%
8/41 • Number of events 13
|
|
Nervous system disorders
Headache
|
14.6%
6/41 • Number of events 8
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
34.1%
14/41 • Number of events 70
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.3%
3/41 • Number of events 5
|
|
Vascular disorders
Hypertension
|
19.5%
8/41 • Number of events 9
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
4.9%
2/41 • Number of events 6
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
26.8%
11/41 • Number of events 37
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
7.3%
3/41 • Number of events 4
|
|
Investigations
INR increased
|
4.9%
2/41 • Number of events 27
|
|
Investigations
Lymphocyte count decreased
|
12.2%
5/41 • Number of events 15
|
|
Gastrointestinal disorders
Nausea
|
4.9%
2/41 • Number of events 2
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
4.9%
2/41 • Number of events 2
|
|
Renal and urinary disorders
Proteinuria
|
22.0%
9/41 • Number of events 20
|
|
Skin and subcutaneous tissue disorders
Rash acneiform
|
4.9%
2/41 • Number of events 2
|
|
Gastrointestinal disorders
Vomiting
|
7.3%
3/41 • Number of events 3
|
|
Investigations
White blood cell decreased
|
4.9%
2/41 • Number of events 16
|
Additional Information
Dr. David Pfister
Memorial Sloan Kettering Cancer Center
Phone: 646-888-4237
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60