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Recurrent Thyroid Gland CarcinomaPhase 2NCT00729157

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

A Phase 2 study testing Fludeoxyglucose F-18, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Thyroid Gland Carcinoma and Stage III Thyroid Gland Follicular Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fludeoxyglucose F-18, Laboratory Biomarker Analysis and Pharmacological Study
Could I receive a placebo?
No, everyone receives an active treatment
How many people
41 participants
Where
1 siteUnited States
Study dates
Aug 2008to Nov 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 65Show fewer
  • 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

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

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

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.

Read the 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.

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.

III. 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.

IV. 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.

II. 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.

Being tested
Fludeoxyglucose F-18, Laboratory Biomarker Analysis, Pharmacological Study, Positron Emission Tomography, Ziv-Aflibercept
Medical subject headings
Thyroid Neoplasms, Adenocarcinoma, Follicular, Thyroid Cancer, Papillary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fludeoxyglucose F-18Radiation

    Also called 18FDG, FDG, fludeoxyglucose F 18, Fludeoxyglucose F18

    Correlative studies

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET SCAN, Positron Emission Tomography Scan

    Correlative studies

  • Ziv-AfliberceptBiological

    Also called AFLIBERCEPT, AVE0005, Vascular Endothelial Growth Factor Trap, VEGF Trap

    Given IV

Study groups in NCT00729157
Study groupRoleWhat they receive
Treatment (ziv-aflibercept and fludeoxyglucose F 18)ExperimentalPatients 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.
Receives: Radiation: Fludeoxyglucose F-18; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Procedure: Positron Emission Tomography; Biological: Ziv-Aflibercept

What is being measured

The primary outcome is the main question the study is designed to answer.

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

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

    Measured: 6 months

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

    Measured: After 8 weeks of study therapy

Secondary outcomes (3)

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

    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.

    Measured: From the beginning of treatment through 30 days until participant comes off study

  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.

    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.

    Measured: 8 weeks

  3. Effect of Thyroglobulin Concentration on Progression-free Survival

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

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionOct 2012
  4. Study completionNov 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
41 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00729157
Sponsor's protocol ID
NCI-2009-00178
Other IDs
NCI-2009-00178, MSKCC-08066, CDR0000608163, 08-066, 7508, N01CM62206, P30CA008748
Status last verified
Jan 2017
First submitted
6 Aug 2008
Last updated
15 Mar 2017
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fludeoxyglucose F-18, Laboratory Biomarker Analysis and Pharmacological Study in people with Recurrent Thyroid Gland Carcinoma and Stage III Thyroid Gland Follicular Carcinoma, run by National Cancer Institute (NCI) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 65 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival to Determine the 6-month Progression-free-survival (PFS) Rate (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00729157.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2017.

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