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

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00729157
• Collaborator: (none)
• Enrollment: 41
• Location: 1
• Arm: 1
• Duration (Months): 51
• Patients Per Site Per Month: 0.8

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
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	Radiation: Fludeoxyglucose F-18; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Positron Emission Tomography; Biological: Ziv-Aflibercept	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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:

1. 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.

2. 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.

3. 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) and progression-free-survival at 6 months after start of therapy in patients with recurrent and/or metastatic D-TC-FCO.

4. 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.

TERTIARY OBJECTIVES:

1. To determine population pharmacokinetics of IV VEGF Trap for patients with thyroid cancer.

2. To determine whether antibodies to VEGF Trap develop in patients with thyroid cancer.

OUTLINE:

Patients receive aflibercept intravenously (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 fludeoxyglucose F 18 (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.

After completion of study therapy, patients are followed up for 2-4 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 41 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Nov 1, 2012

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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.

Radiation: Fludeoxyglucose F-18; Correlative studies; Other Names: 18FDG FDG fludeoxyglucose F 18 Fludeoxyglucose F18 Fluorine-18 2-Fluoro-2-deoxy-D-Glucose Fluorodeoxyglucose F18 ; Other: Laboratory Biomarker Analysis; Correlative studies; Other: Pharmacological Study; Correlative studies; Procedure: Positron Emission Tomography; Correlative studies; Other Names: Medical Imaging, Positron Emission Tomography PET PET SCAN Positron Emission Tomography Scan Positron-Emission Tomography proton magnetic resonance spectroscopic imaging ; Biological: Ziv-Aflibercept; Given IV; Other Names: AFLIBERCEPT AVE0005 Vascular Endothelial Growth Factor Trap VEGF Trap VEGF Trap R1R2 VEGF-Trap Zaltrap

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate [6 months]

   Progression-free survival to determine the 6-month progression-free-survival (PFS) rate

2. Radiographic Response Rate of Aflibercept in Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy [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

Secondary Outcome Measures

1. 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]

   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.

2. 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]

   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.

3. Effect of Thyroglobulin Concentration on Progression-free Survival [6 months]

   The change is serum thyroglobulin was measured by the percent change between the baseline value and the lowest value obtained while on treatment.

Other Outcome Measures

1. 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. [Baseline-6 months post treatment]

   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.

2. 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) [8 weeks]

   This part is currently under data analysis, therefore, this outcome measure has not been calculated

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: David Pfister, Memorial Sloan Kettering Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00729157
• Other Study ID Numbers: NCI-2009-00178; NCI-2009-00178; MSKCC-08066; CDR0000608163; 08-066; 7508; N01CM62206; P30CA008748
• First Posted: Aug 7, 2008
• Last Update Posted: Mar 15, 2017
• Last Verified: Jan 1, 2017

• Additional relevant MeSH terms: Carcinoma; Thyroid Neoplasms; Carcinoma, Papillary; Thyroid Cancer, Papillary; Adenocarcinoma, Follicular; Thyroid Diseases; Recurrence; Deoxyglucose; Aflibercept; Endothelial Growth Factors; Fluorodeoxyglucose F18

Study Results

Participant Flow

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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

Baseline Characteristics

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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 Participants	41
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 48.8%
>=65 years	21 51.2%
Sex: Female, Male (Count of Participants)
Female	22 53.7%
Male	19 46.3%
Region of Enrollment (participants) [Number]
United States	41 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate
Description	Progression-free survival to determine the 6-month progression-free-survival (PFS) rate
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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.
Measure Participants	18
Median (95% Confidence Interval) [months]	5.4

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
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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.
Measure Participants	40
Progression of Disease	7 17.1%
Stable Disease	33 80.5%

3. Secondary Outcome

Title	The Safety and Toxicity Profile of IV VEGF Trap in Patients With Recurrent and/or Metastatic TC-FCO
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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.
Measure Participants	41
Number [participants]	36 87.8%

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.
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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.
Measure Participants	8
Median (95% Confidence Interval) [percent of SUVm change]	.64

5. Secondary Outcome

Title	Effect of Thyroglobulin Concentration on Progression-free Survival
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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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.
Measure Participants	36
Median (Full Range) [percent change serum thyroglobulin]	0.4

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.
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

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

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)
Description	This part is currently under data analysis, therefore, this outcome measure has not been calculated
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
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 (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
	Affected / at Risk (%)	# Events
Total	24/41 (58.5%)
Blood and lymphatic system disorders
Anemia	1/41 (2.4%)	1
Cardiac disorders
Cardiac disorder	1/41 (2.4%)	1
Myocardial infarction	2/41 (4.9%)	2
Endocrine disorders
Hyperthyroidism	1/41 (2.4%)	1
Gastrointestinal disorders
Diarrhea	1/41 (2.4%)	1
Dysphagia	2/41 (4.9%)	3
Duodenal hemorrhage	1/41 (2.4%)	1
Nausea	1/41 (2.4%)	1
Abdominal pain	1/41 (2.4%)	1
Anal pain	1/41 (2.4%)	1
General disorders
Death not assoc w CTCAE term-Disease prog NOS	2/41 (4.9%)	2
Edema: limb	1/41 (2.4%)	1
Fatigue	2/41 (4.9%)	2
Non-cardiac Chest pain	2/41 (4.9%)	2
Infections and infestations
Urinary tract infection	1/41 (2.4%)	1
Investigations
Lymphocyte count decrease	5/41 (12.2%)	5
Platelet count decrease	1/41 (2.4%)	1
Metabolism and nutrition disorders
Hypocalcemia	2/41 (4.9%)	2
Hypermagnesemia	1/41 (2.4%)	1
Musculoskeletal and connective tissue disorders
Joint disorder	4/41 (9.8%)	4
Muscle weakness upper limb	4/41 (9.8%)	4
Back pain	1/41 (2.4%)	1
Buttock pain	1/41 (2.4%)	1
Pain in extremity	1/41 (2.4%)	1
Neck pain	2/41 (4.9%)	2
Nervous system disorders
Cerebrovascular ischemia	1/41 (2.4%)	1
Neurological disorder	1/41 (2.4%)	1
Peripheral sensory neuropathy	1/41 (2.4%)	2
Headache	2/41 (4.9%)	2
Syncope	1/41 (2.4%)	1
Psychiatric disorders
Confusion	2/41 (4.9%)	2
Renal and urinary disorders
Proteinuria	5/41 (12.2%)	5
Renal failure	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnea	3/41 (7.3%)	4
Pneumonia	1/41 (2.4%)	1
Pleural effusion	2/41 (4.9%)	2
Vascular disorders
Hematoma	1/41 (2.4%)	1
Hypertension	3/41 (7.3%)	3
Hypotension	2/41 (4.9%)	2
Thrombosis	1/41 (2.4%)	1
Thrombotic microangiopathy	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)
	Affected / at Risk (%)	# Events
Total	36/41 (87.8%)
Blood and lymphatic system disorders
Anemia	2/41 (4.9%)	4
Gastrointestinal disorders
Dysphagia	3/41 (7.3%)	3
Nausea	2/41 (4.9%)	2
Vomiting	3/41 (7.3%)	3
General disorders
Fatigue	8/41 (19.5%)	13
Investigations
Blood bilirubin increased	4/41 (9.8%)	11
INR increased	2/41 (4.9%)	27
Lymphocyte count decreased	5/41 (12.2%)	15
White blood cell decreased	2/41 (4.9%)	16
Metabolism and nutrition disorders
Anorexia	4/41 (9.8%)	4
Hyperglycemia	14/41 (34.1%)	70
Hyperkalemia	3/41 (7.3%)	5
Hypoalbuminemia	2/41 (4.9%)	6
Hypocalcemia	11/41 (26.8%)	37
Hypophosphatemia	3/41 (7.3%)	4
Musculoskeletal and connective tissue disorders
Arthralgia	7/41 (17.1%)	11
Bone pain	2/41 (4.9%)	2
Nervous system disorders
Headache	6/41 (14.6%)	8
Peripheral sensory neuropathy	2/41 (4.9%)	2
Renal and urinary disorders
Proteinuria	9/41 (22%)	20
Respiratory, thoracic and mediastinal disorders
Cough	5/41 (12.2%)	6
Skin and subcutaneous tissue disorders
Rash acneiform	2/41 (4.9%)	2
Vascular disorders
Hypertension	8/41 (19.5%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.