Symptoms and General Pathology

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Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

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Adenocarcinoma

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Neoplasms by Histologic Type

Disease Attributes

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Papillary Thyroid Carcinoma

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Fluorodeoxyglucose F18

Aflibercept

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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.

Fludeoxyglucose F-18

Laboratory Biomarker Analysis

Pharmacological Study

Positron Emission Tomography

Ziv-Aflibercept

David Pfister

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.

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.

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:

I. 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.

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

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 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.

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

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

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

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.

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.

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

National Cancer Institute (NCI)

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.

Treatment (Ziv-aflibercept and Fludeoxyglucose F 18)

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Dr. David Pfister

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

Progression of Disease

Stable Disease

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

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

Effect of Thyroglobulin Concentration on Progression-free Survival

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.

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)

Overall Study

Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.

Selumetinib

David Neil Hayes

This phase II trial is studying how well selumetinib works in treating patients with papillary thyroid cancer that did not respond to radioactive iodine. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PRIMARY OBJECTIVES:

I. Ascertain the objective response rate (complete response and partial response) in patients with iodine I 131-refractory papillary thyroid cancer treated with selumetinib.

SECONDARY OBJECTIVES:

I. Determine the toxicity of this treatment in these patients. II. Determine the pharmacokinetic profile of this treatment in these patients. III. Determine the progression-free and overall survival of these patients. IV. Assess proxy measures of treatment response (thyroglobulin and PET scan) in patients treated with selumetinib.

IV. Compare relevant laboratory correlates between responders and non-responders.

OUTLINE: This is a multicenter study.

Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Archived tissue is examined for gene mutations, including RET, BRAF, NTRK, and RAS, by fluorescence in situ hybridization and/or polymerase chain reaction and fluorescence melting curve analysis. Protein expression of ERK and phosphorylated ERK is assessed by immunohistochemical staining.

Blood samples are collected periodically for pharmacokinetic analysis and biomarker assessment (thyroglobulin and antithyroglobulin autoantibodies).

After completion of study therapy, patients are followed periodically for up to 2 years.

Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine

Phase 2 Study of Selumetinib Hydrogen Sulfate in Iodine-131 Refractory Papillary Thyroid Carcinoma and Papillary Thyroid Carcinoma With Follicular Elements

ORR: Complete Response (CR) and Partial Response (PR) evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. A conservative estimate of the response rate of the best-studied agent in this disease, doxorubicin, is approximately 5%. Therefore, investigators will assume that selumetinib (AZD6244, NSC 741078) would be worth further pursuit if the response rate (CR+PR) were at least 20%.

PFS is defined as the duration of time from start of treatment to time of progression or death. Progression evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST). Progressive Disease (PD): 20% increase in the sum of appropriate diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, as well as an absolute increase of at least 0.5 cm. Secondary end points include toxicity, progression free survival, and overall survival. Due to the small sample size and absence of high quality historic data for this disease, these analyses were planned to be mostly exploratory and descriptive in nature.

Number of participants with related adverse events, per category and Grade category. Toxicity assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

Overall Survival using the Kaplan-Meier method with associated confidence intervals. OS analysis was intended to be mostly exploratory and descriptive in nature.

All participants were evaluated for adverse events.

All Participants

Patients receive oral selumetinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of unacceptable toxicity or disease progression.

Laboratory Biomarker Analysis: Correlative studies

Selumetinib: Selumetinib was administered orally as a free base suspension at a dose of 100 mg twice daily for 28-day cycles. Those participants experiencing Common Terminology Criteria for Adverse Events (CTCAE) v3.0 grade 3 toxicity or worse had their dose reduced to 50 mg twice daily and then to 50 mg once daily, if necessary.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy	NCT00729157	Recurrent Thyro... Stage III Thyro... Stage III Thyro... Stage IV Thyroi... Stage IV Thyroi...	Fludeoxyglucose... Laboratory Biom... Pharmacological... Positron Emissi... Ziv-Aflibercept	18 Years -	National Cancer Institute (NCI)
Aflibercept in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy	NCT00729157	Recurrent Thyro... Stage III Thyro... Stage III Thyro... Stage IV Thyroi... Stage IV Thyroi...	Fludeoxyglucose... Laboratory Biom... Pharmacological... Positron Emissi... Ziv-Aflibercept	18 Years -	National Cancer Institute (NCI)
Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine	NCT00559949	Recurrent Thyro... Stage I Thyroid... Stage II Thyroi... Stage III Thyro... Stage IV Thyroi...	Laboratory Biom... Selumetinib	18 Years -	National Cancer Institute (NCI)
Selumetinib in Treating Patients With Papillary Thyroid Cancer That Did Not Respond to Radioactive Iodine	NCT00559949	Recurrent Thyro... Stage I Thyroid... Stage II Thyroi... Stage III Thyro... Stage IV Thyroi...	Laboratory Biom... Selumetinib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iv thyroid gland papillary carcinoma