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

Carcinoma, Medullary

Carcinoma, Neuroendocrine

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Neoplasms, Squamous Cell

Adenocarcinoma, Papillary

Papillary Thyroid Carcinoma

Thyroid Cancer, Medullary

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Anti-Infective Agents

Sunitinib

Iodine

Cadexomer iodine

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Patients receive sunitinib malate PO QD on days 1-28. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

Laboratory Biomarker Analysis

Pharmacogenomic Study

Sunitinib Malate

Tanguy Y Seiwert

This phase II trial studies how well sunitinib malate works in treating patients with thyroid cancer that did not respond to iodine I 131 (radioactive iodine) and cannot be removed by surgery. Sunitinib malate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. Determine the response rate of single agent sunitinib (sunitinib malate) in patients with iodine refractory, unresectable well-differentiated thyroid cancer (WDTC) who have evidence of disease progression within 6 months of study enrollment.

II. Determine the response rate of single agent sunitinib in patients with medullary thyroid cancer (MTC) who have evidence of disease progression within 6 months of study enrollment.

III. Determine the toxicity, duration of response, progression free survival, and overall survival in patients with WDTC or MTC treated with single agent sunitinib.

IV. Determine whether the presence of ret proto-oncogene (RET) gene rearrangements in patients with WDTC or RET mutations in patients with MTC predict response to sunitinib.

V. Determine whether therapy with sunitinib affects phosphorylation of downstream RET effector, mitogen-activated protein kinase 1 (ERK), in WDTC and MTC tissue.

VI. Determine whether specific germ-line polymorphisms in the RET gene are associated with favorable outcome in patients with WDTC treated with sunitinib.

OUTLINE: Patients are assigned to 1 of 2 cohorts according to type of thyroid cancer (medullary vs well-differentiated).

Patients receive sunitinib malate orally (PO) once daily (QD) on days 1-28. Cycles repeat every 6 weeks in the absence of disease progression or unacceptable toxicity.

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

Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery

Phase II Trial of Sunitinib (SU11248) in Iodine-131 Refractory, Unresectable Differentiated Thyroid Cancers and Medullary Thyroid Cancers

Relevant laboratory correlates will be compared between responders and non-responders using the Wilcoxon rank sum test. The association between the presence or absence of RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorphisms in the RET gene and response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as covariates (univariate analyses only due to the small sample size) in a Cox regression model of progression-free survival.

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CT or 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."

Any grade toxicity of any type, regardless of attribution

Kaplan-Meier curves will be generated and 95% confidence intervals will be derived for median overall survival.

National Cancer Institute (NCI)

Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

This arm contains results for the Radioactive Iodine Refractory Thyroid Cancer Subgroup

Sunitinib Malate: Given PO

Sunitinib Malate-Radioactive Iodine Refractory Subgroup

Patients receive sunitinib malate PO QD on days 1-28. Courses repeat every 6 weeks in the absence of disease progression or unacceptable toxicity

This arm contains results for the Metastatic Medullary Thyroid Cancer Subgroup

Sunitinib Malate: Given PO

Sunitinib Malate-Metastatic Medullary Subgroup

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

Dr. Tanguy Seiwert

Note. The objective was not to compare the two arms (subgroups), but to compare each with historical data.

Objective Response Rate, Assessed Using the Response Evaluation Criteria in Solid Tumors (RECIST)

Incidence of Toxicity, Graded According to the Common Terminology Criteria for Adverse Events Version 3.0

Overall Survival

Time to Progression or Death Evaluated Using the RECIST

Changes in Laboratory Correlates Analyzed Using Paired T-tests

Overall Study

Diseases and Abnormalities at or Before Birth

Multiple Endocrine Neoplasia

Multiple Endocrine Neoplasia Type 2a

Multiple Endocrine Neoplasia Type 2b

Neoplasms, Multiple Primary

Syndrome

Neoplastic Syndromes, Hereditary

Genetic Diseases, Inborn

Multiple Endocrine Neoplasia Type 2

Multiple Endocrine Neoplasia Type 2A

Multiple Endocrine Neoplasia Type 2B

Sorafenib

Patients receive sorafenib tosylate PO BID in the absence of disease progression or unacceptable toxicity.

Sorafenib Tosylate

Bhavana Konda

This phase II trial studies how well sorafenib tosylate works in treating patients with medullary thyroid cancer that has spread to other parts of the body (metastatic), spread to the tissue surrounding the thyroid (locally advanced), or has returned after a period of improvement (recurrent). Sorafenib tosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

PRIMARY OBJECTIVES:

I. To assess objective response rate of sorafenib tosylate (sorafenib \[BAY 43-9006\]) in metastatic medullary thyroid carcinoma in setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC).

II. To assess objective response rate of sorafenib (BAY 43-9006) in sporadic metastatic medullary thyroid carcinoma.

SECONDARY OBJECTIVES:

I. To assess toxicity of sorafenib (BAY 43-9006) in patients with metastatic medullary thyroid carcinoma.

II. Measure serum tumor markers calcitonin and carcinoembryonic antigen (CEA) pre-, during, and post-treatment to correlate with disease response.

III. Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 \[F-18 fluorodeoxyglucose\] positron emission tomography \[PET\] scan) data obtained at pre-, during, and post-treatment with tumor response.

IV. Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained at pre-, during, and post-treatment with changes in tumor permeability and vascularity with tumor response.

V. Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed.

VI. To correlate between the degree of retrovirus-associated sequence (Ras)-mitogen-activated protein kinase (MAPK) signaling inhibition and vascular endothelial growth factor (VEGF) expression in the tumor and clinical response.

VII. To correlate between the presence and type of ret proto-oncogene (RET) gene defects in tumor and clinical response.

OUTLINE:

Patients receive sorafenib tosylate orally (PO) twice daily (BID) in the absence of disease progression or unacceptable toxicity.

Sorafenib Tosylate in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer

Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma

Measured using MRI scans. Determined using Response Evaluation Criteria in Solid Tumors/World Health Organization response criteria. 95% confidence interval will be calculated to estimate the frequency of response.

Identifying the number of patients with decreased calcitonin levels

Identify the number of patients with decreased Carcinoembryonic Antigen (CEA) levels

Median decrease in exchange rate Kep in index lesions

Identify the number of patients with degree of Ras-MAPK signaling inhibition

Identify the median SUV at baseline and 8 week follow up as measured by Fludeoxyglucose F-18 Positron Emission Tomography (PET).

Toxicities were graded for patients using the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0

Changes will be correlated with toxicity and clinical response to therapy.

The National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was utilized for adverse event reporting

Arm A:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm B:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm A (Hereditary MTC) and Arm B (Sporadic MTC)

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm A (Hereditary MTC)

Arm B (Sporadic MTC)

Age, Categorical

White

Nonwhite

Race/Ethnicity, Customized

Manisha Shah, MD

1 patient was not evaluable for RECIST evaluation in Arm B

Objective Response Rate of Sorafenib Tosylate in Metastatic Medullary Thyroid Carcinoma in Setting of Inherited Tumor Syndromes as Well as in Setting of Sporadic Medullary Thyroid Cancer

Arm A:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Arm B:

Sorafenib (BAY 43-9006) was administered at the dose of 400 mg orally twice a day on a continuous basis.

Number of Patients With Decreased Calcitonin Levels

Patient With Decreased Carcinoembryonic Antigen (CEA) Levels

Percent of Baseline Dynamic-Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) Exchange Rate Constant (Kep)

Due to low tumor cellularity in the samples obtained, such evaluation was not possible

Degree of Ras-MAPK Signaling Inhibition in the Tumor

MTC in setting of inherited syndromes (MEN-2A, 2B or FMTC) plus Measurable disease Plus No prior ZD6474 or AMG 706

Arm A

MTC in setting of sporadic ds plus Measurable disease Plus No prior ZD6474 or AMG 706

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Sunitinib Malate in Treating Patients With Thyroid Cancer That Did Not Respond to Iodine I 131 and Cannot Be Removed by Surgery	NCT00381641	Differentiated ... Recurrent Thyro... Refractory Thyr... Stage III Thyro... Stage III Thyro... Stage IV Thyroi... Stage IV Thyroi... Stage IV Thyroi... Stage IVA Thyro... Stage IVA Thyro... Stage IVA Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVB Thyro... Stage IVC Thyro... Stage IVC Thyro... Stage IVC Thyro... Thyroid Gland O... Unresectable Th...	Laboratory Biom... Pharmacogenomic... Sunitinib Sunitinib Malat...	18 Years -	National Cancer Institute (NCI)
Sorafenib Tosylate in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer	NCT00390325	Hereditary Thyr... Locally Advance... Multiple Endocr... Multiple Endocr... Recurrent Thyro... Sporadic Thyroi... Stage III Thyro... Stage IV Thyroi... Stage IVA Thyro... Stage IVB Thyro... Stage IVC Thyro...	Sorafenib Tosyl...	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for stage iv thyroid gland medullary carcinoma ajcc v7