Sorafenib in Treating Patients With Metastatic, Locally Advanced, or Recurrent Medullary Thyroid Cancer - Full Text View

Sponsors and Collaborators:	Arthur G. James Cancer Hospital & Richard J. Solove Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00390325

Purpose

RATIONALE: Sorafenib 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.

PURPOSE: This phase II trial is studying how well sorafenib works in treating patients with metastatic, locally advanced, or recurrent medullary thyroid cancer.

Condition	Intervention	Phase
Head and Neck Cancer Multiple Endocrine Neoplasia 1 and 2 (men1, men2)	Drug: sorafenib tosylate Procedure: immunohistochemistry staining method Procedure: laboratory biomarker analysis Procedure: molecular genetic technique Procedure: mutation analysis Procedure: pharmacological study	Phase II

Genetics Home Reference related topics: multiple endocrine neoplasia

MedlinePlus related topics: Cancer Head and Neck Cancer Thyroid Cancer

Drug Information available for: Sorafenib Sorafenib tosylate Thyroid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Objective response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Correlation of serum tumor markers calcitonin and carcinoembryonic antigen (CEA) measurements with disease response at baseline, every 8 weeks during treatment, and after completion of treatment [ Designated as safety issue: No ]
Correlation of nuclear medicine functional imaging data by fludeoxyglucose F 18 positron emission tomography (PET) scan with tumor response [ Designated as safety issue: No ]
Correlation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data with changes in tumor permeability and vascularity and tumor response [ Designated as safety issue: No ]
Pharmacogenomics on procured peripheral blood mononuclear cells (PBMCs) in the setting of clinical response [ Designated as safety issue: No ]
Correlation of the degree of Ras-MAPK signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response [ Designated as safety issue: No ]
Correlation of the presence and type of RET gene defects in the tumor with clinical response [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	October 2006
Estimated Primary Completion Date:	February 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine objective response rate in patients with metastatic, locally advanced, or recurrent medullary thyroid carcinoma in a setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC), treated with sorafenib tosylate.
Determine objective response rate in patients with sporadic metastatic medullary thyroid carcinoma treated with sorafenib tosylate.

Secondary

Determine toxicity of sorafenib in these patients.
Measure serum tumor markers calcitonin and carcinoembryonic antigen (CEA) pre-, during, and post-treatment and correlate with disease response in these patients.
Correlate nuclear medicine functional imaging (fludeoxyglucose F 18 positron emission tomography [PET] scan) data obtained at pre-, during, and post-treatment with tumor response in these patients.
Correlate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data obtained at pre-, during, and post-treatment with changes in tumor permeability and vascularity and tumor response in these patients.
Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed in these patients.
Correlate the degree of Ras-MAPK signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response in these patients.
Correlate the presence and type of RET gene defects in tumor with clinical response in these patients.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical setting of disease (inherited tumor syndromes vs sporadic).

Patients receive oral sorafenib tosylate twice daily on days 1-56. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity.

Patients undergo blood collection and tumor biopsies for biomarker/laboratory studies (immunohistochemistry, pharmacogenomic studies, and genotyping) at baseline, every 8 weeks during treatment, and after completion of study treatment. Tumor markers may include carcinoembryonic antigen (CEA), calcitonin, and RET mutations.

After completion of study treatment, patients are followed for 4 weeks.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed medullary thyroid carcinoma (MTC) meeting 1 of the following criteria:
- Inherited tumor syndromes (e.g., multiple endocrine neoplasia [MEN] 2A, MEN 2B, or familial medullary thyroid carcinoma [FMTC])
- Sporadic MTC
Metastatic and/or locally advanced or locally recurrent disease
Measurable disease

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 6 months
WBC ≥ 2,000/mm³
Absolute neutrophil count ≥ 1,000/mm³
Platelet count ≥ 100,000/mm³
Bilirubin ≤ 2 times upper limit of normal (ULN)
AST and ALT ≤ 3 times ULN
Creatinine normal OR creatinine clearance > 30 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib tosylate
No condition that impairs ability to swallow pills
No uncontrolled intercurrent illness, including, but not limited to, any of the following:
- Ongoing or active infection
- Uncontrolled hypertension
- Psychiatric illness or social situation that would preclude study compliance
No evidence of a bleeding diathesis

PRIOR CONCURRENT THERAPY:

At least 4 weeks since prior systemic antitumor therapy (e.g., chemotherapy, biologic modifiers, or antiangiogenic therapy) (6 weeks for nitrosourea or mitomycin C)
More than 1 week since prior external beam radiotherapy and recovered
No prior sorafenib, ZD6474, or AMG-706
No other concurrent tumor-specific therapy for thyroid cancer or investigational therapy
Concurrent adjuvant hormonal therapy for a second primary (e.g., breast cancer or prostate cancer) allowed if no known drug interactions
Concurrent oral or IV bisphosphonates allowed for patients with bone metastases
No concurrent active anticoagulation with therapeutic intent
- Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial access devices allowed provided the PT, INR, or PTT are normal
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital), rifampin, or Hypericum perforatum (St. John's wort)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390325

Locations

United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Jeffrey F. Moley, MD 314-747-0064
United States, Ohio
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center	Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Manisha H. Shah, MD 614-293-8629 manisha.shah@osumc.edu

Sponsors and Collaborators

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Manisha H. Shah, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000507441, OSU-06054, NCI-7609
Study First Received:	October 18, 2006
Last Updated:	October 22, 2008
ClinicalTrials.gov Identifier:	NCT00390325
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

thyroid gland medullary carcinoma
recurrent thyroid cancer
multiple endocrine neoplasia 1 and 2 (MEN1, MEN2)

Study placed in the following topic categories:

Carcinoma, Medullary
Thyroid Neoplasms
Endocrine System Diseases
Recurrence
Carcinoma
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn

Head and Neck Neoplasms
Thyroid cancer, medullary
Multiple Endocrine Neoplasia
Endocrinopathy
Sorafenib
Thyroid Diseases
Endocrine Gland Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses

Neoplasms, Multiple Primary
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 15, 2009