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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00390325
First received: October 18, 2006
Last updated: February 7, 2014
Last verified: February 2014
  Purpose

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


Condition Intervention Phase
Multiple Endocrine Neoplasia
Recurrent Thyroid Cancer
Thyroid Gland Medullary Carcinoma
Drug: sorafenib tosylate
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 [ Time Frame: Every 12 weeks ] [ Designated as safety issue: No ]
    Measured using MRI scans. Determined using RECIST/WHO response criteria. 95% confidence interval will be calculated to estimate the frequency of response.


Secondary Outcome Measures:
  • Toxicity of sorafenib in patients with metastatic medullary thyroid carcinoma [ Time Frame: From the time of their first treatment with sorafenib ] [ Designated as safety issue: Yes ]
    Graded using the revised National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.

  • Correlation of serum tumor markers calcitonin and carcinoembryonic antigen (CEA) measurements with disease response [ Time Frame: Baseline, every 12 weeks during treatment, and 2-4 weeks after completion of treatment ] [ Designated as safety issue: No ]
    95% confidence interval will be calculated.

  • Correlation of nuclear medicine functional imaging data with tumor response [ Time Frame: Baseline and every 12 weeks during treatment ] [ Designated as safety issue: No ]
    Measured by by fludeoxyglucose F-18 positron emission tomography (PET) scan. 95% confidence interval will be calculated.

  • Correlation of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) data with changes in tumor permeability and vascularity and tumor response [ Time Frame: Baseline and every 12 weeks during treatment ] [ Designated as safety issue: No ]
    MRI scans will be utilized to measure response. 95% confidence interval will be calculated.

  • Pharmacogenomics on procured peripheral blood mononuclear cells (PBMCs) in the setting of clinical response [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    We will examine for selected polymorphisms of genes influencing sorafenib metabolism and/or resistance genes that may predict response or toxicity.

  • Correlation of the degree of Ras-MAPK signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response [ Time Frame: Baseline, at 12 weeks, and within 4 weeks after completion of treatment ] [ Designated as safety issue: No ]
    Perform MAP kinase and AKT phosphorylation assay by immunohistochemistry.

  • Correlation of the presence and type of RET gene defects in the tumor with clinical response [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Ten micron/slice will be cut from the tumor paraffin tissue block and such 3-4 unstained slides will be used for isolating tumor DNA.


Estimated Enrollment: 50
Study Start Date: October 2006
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (enzyme inhibitor therapy)
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.
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. 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.

II. Determine objective response rate in patients with sporadic metastatic medullary thyroid carcinoma treated with sorafenib tosylate.

SECONDARY OBJECTIVES:

I. 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.

II. 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.

III. 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.

IV. Perform pharmacogenomic studies on procured peripheral blood mononuclear cells (PBMCs) if clinical responses are observed in these patients.

V. Correlate the degree of Ras-MAPK signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response in these patients.

VI. 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.

.

  Eligibility

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

Inclusion Criteria:

  • 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
  • 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
  • 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, Ohio
Ohio State University Medical Center
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Investigators
Principal Investigator: Manisha Shah Ohio State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00390325     History of Changes
Obsolete Identifiers: NCT01645631
Other Study ID Numbers: NCI-2009-00196, NCI-2009-00196, CDR0000507441, OSU 06054 / IRB 2006C0050, 7609, P30CA016058, N01CM62207
Study First Received: October 18, 2006
Last Updated: February 7, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms
Carcinoma
Thyroid Neoplasms
Endocrine Gland Neoplasms
Multiple Endocrine Neoplasia
Thyroid Diseases
Carcinoma, Medullary
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms by Site
Head and Neck Neoplasms
Endocrine System Diseases
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Genetic Diseases, Inborn
Carcinoma, Neuroendocrine
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Adenocarcinoma
Neoplasms, Ductal, Lobular, and Medullary
Neoplasms, Nerve Tissue
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014