Symptoms and General Pathology

All Conditions

Neoplasms

Gland and Hormone Related Diseases

Rare Diseases

Recurrence

Carcinoma

Thyroid Neoplasms

Thyroid Cancer, Papillary

Carcinoma, Papillary

Thyroid Diseases

Adenocarcinoma, Follicular

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Disease Attributes

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neoplasms, Squamous Cell

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Micronutrients

Antibodies

Fluorides

Fluorodeoxyglucose F18

Aflibercept

Immunoglobulins

Endothelial Growth Factors

Mitogens

Deoxyglucose

Iodine

Cadexomer iodine

Angiogenesis Inhibitors

Growth Inhibitors

Radiopharmaceuticals

Antimetabolites

Antiviral Agents

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

Blood and Lymph Conditions

Immune System Diseases

Leukemia-Lymphoma, Adult T-Cell

Adult T-cell Leukemia/lymphoma

Patients receive cabozantinib-s-malate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib S-malate

Manisha Shah

This phase II trial studies how well cabozantinib-s-malate works in treating patients with thyroid cancer that does not respond to treatment. Cabozantinib-s-malate may stop the growth of thyroid cancer by blocking some of the enzymes needed for cell growth. Cabozantinib-s-malate may also stop the growth of thyroid cancer by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. The objective response rate, defined as the proportion of patients who have had a partial response (PR) or complete response (CR) within the first 6 months after initiation of therapy with cabozantinib (cabozantinib-s-malate).

SECONDARY OBJECTIVES:

I. To assess duration of objective response, progression-free survival and overall survival.

II. To assess tolerability and adverse events of cabozantinib as a 2nd line therapy in patients with differentiated thyroid cancer (DTC).

TERTIARY OBJECTIVES:

I. To assess effect of cabozantinib on serum tumor marker thyroglobulin and its correlation with overall response rate.

II. To assess response of cabozantinib in bone metastasis (bone metastasis-specific progression free survival) as evaluated by pre- and on-study functional imaging such as bone scan, fludeoxyglucose F 18 (18F-FDG) positron emission tomography (PET) scan and/or 18F sodium fluoride (NaF) PET scan.

III. To assess effect of cabozantinib on serum and urinary markers of bone turnover and its correlation with response to bone metastasis.

IV. To assess predictors of response by performing tumor genotype studies (e.g. v-raf murine sarcoma viral oncogene homolog B \[BRAF\], rat sarcoma \[RAS\], phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha \[PIK3CA\], mitogen-activated protein kinase 1 \[MAP2K1\], v-akt murine thymoma viral oncogene homolog 1 \[AKT1\], mesenchymal-epithelial transition \[MET\], rearranged in transformation \[RET\]/papillary thyroid carcinoma \[PTC\] rearrangement) in archived tumor tissue.

V. To assess predictors of response by assessing baseline expression levels of vascular endothelial growth factor (VEGF), phosphorylated vascular endothelial growth factor receptor (pVEGFR), phosphorylated mitogen-activated protein kinase 1 (pERK), phosphorylated AKT1 (pAKT) and/or total met proto-oncogene (MET) by immunohistochemistry in archived tumor tissue.

OUTLINE:

Patients receive cabozantinib-s-malate orally (PO) daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 3 months for 1 year.

Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer

Phase II Study of Cabozantinib in Patients With Radioiodine-Refractory Differentiated Thyroid Cancer Who Progressed on Prior VEGFR-Targeted Therapy

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and 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 + PR

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

These baseline levels will be quantitatively summarized and graphically explored, in particular in terms of how they relate to clinical outcomes of interest. Analyses exploring differences in these angiogenic and correlative markers in relation to clinical outcomes will be largely hypothesis-generating. With limited numbers of patients patterns of difference will primarily be looked for using graphical analyses; these can include plots of these marker levels in relation to clinical outcomes to identify potential patterns of interest.

The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. Tolerability of the regimens will be assessed through assessing the number of patients who required dose modifications and/or dose delays. In addition, the proportion of patients who go off treatment due to adverse reactions or even those who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial will be captured.

Side-by-side boxplots will be used to assess possible differences in this change between responders and non-responders, and scatterplots can assess the influence of baseline thyroglobulin levels on these measures of change.

Exelixis

The National Cancer Institutes (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was utilized for Adverse event reporting.

Patients receive cabozantinib-s-malate PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cabozantinib S-malate: Given PO

Laboratory Biomarker Analysis: Correlative studies

Treatment (Cabozantinib-s-malate)

Patients receive Cabozantinib 60mg PO QD with dose escalation to 80mg QD or dose reduction to 40mg daily or 20mg. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Age, Continuous

Race (NIH/OMB)

Manisha Shah, MD

Objective Response Rate, Defined as the Proportion of Patients Who Have Had a PR or CR as Assessed by the RECIST Version (v)1.1

Data not collected to be analyzed at this time

Bone Turnover, as Measured by Serum and Urinary Markers of Bone Turnover

Duration of Objective Response as Assessed by the RECIST v1.1

Data has not been collected and analyzed at this time

Expression Levels of Predictive Biomarkers of Response by Immunohistochemistry in Archived Tumor Tissue

Genotype of Biomarkers Potentially Predictive of Response

Left ventricular systolic dysfunction

asymptomatic increased lipase

osteonecrosis of the jaw

decubitus ulcer

pneumonia

meningitis

perianal hidradenitis suppurativa

Incidence of Severe (Grade 3+) Adverse Events, Graded According to the National Cancer Institute CTCAE v4.0

Overall Survival

Percent Change in Serum Tumor Marker Thyroglobulin Levels

Progression-free Survival

Response of Cabozantinib-s-malate in Bone Metastasis (Bone Metastasis-specific Progression Free Survival) as Evaluated by Functional Imaging

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)
Cabozantinib-S-Malate in Treating Patients With Refractory Thyroid Cancer	NCT01811212	Poorly Differen... Recurrent Thyro... Stage I Thyroid... Stage I Thyroid... Stage II Thyroi... Stage II Thyroi... Stage III Thyro... Stage III Thyro... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Thyro... Stage IVC Thyro... Tall Cell Varia... Thyroid Gland O...	Cabozantinib S-... Laboratory Biom...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iii thyroid gland follicular carcinoma