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: September 30, 2014
Last verified: September 2014
  Purpose

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.


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: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence of toxicity, graded using the revised National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: Yes ]
  • Calcitonin levels [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    Correlated with disease response.

  • CEA levels [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    Correlated with disease response.

  • Fludeoxyglucose F-18 PET data [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    Correlated with tumor response.

  • DCE-MRI data [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    Correlated with tumor response.

  • Selected polymorphisms of genes influencing sorafenib tosylate metabolism and/or resistance genes that may predict response or toxicity [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Changes will be correlated with toxicity and clinical response to therapy.

  • Degree of Ras-MAPK signaling inhibition in the tumor [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    Correlated with clinical response.

  • Degree of VEGF expression in the tumor [ Time Frame: Up to 4 weeks after last dose of sorafenib tosylate ] [ Designated as safety issue: No ]
    Correlated with clinical response.

  • RET gene defects in the tumor [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Presence and type will be correlated with clinical response.


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 (sorafenib tosylate)
Patients receive sorafenib tosylate PO BID 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. To assess objective response rate of sorafenib (BAY 43-9006) (sorafenib tosylate) 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.

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 with tumor response.

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

V. To correlate between the degree of retrovirus-associated deoxyribonucleic acid (DNA) sequences (Ras)-mitogen-activated protein kinase (MAPK) signaling inhibition with vascular endothelial growth factor (VEGF) expression in the tumor and clinical response.

VI. 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) on days 1-56. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity.

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:

  • ELIGIBILITY CRITERIA SPECIFIC FOR ARM A
  • Histologically confirmed medullary thyroid carcinoma under the clinical setting of inherited tumor syndromes, such as multiple endocrine neoplasia (MEN) 2A, MEN 2B, or familial medullary thyroid carcinoma (FMTC)
  • ELIGIBILITY CRITERIA SPECIFIC FOR ARM B
  • Histologically confirmed medullary thyroid carcinoma under the clinical setting of sporadic medullary thyroid carcinoma (MTC)
  • ELIGIBILITY CRITERIA COMMON FOR ARMS A AND B
  • Patients must have measurable disease
  • Metastatic and/or locally advanced or locally recurrent disease
  • Oral or intravenous (IV) bisphosphonates therapy will be allowed for patients with bony metastasis at the investigator's discretion; bisphosphonate usage should be recorded if used
  • Life expectancy must be >= six months
  • Patients must have an Eastern Cooperative Oncology Group performance status 0-2
  • Leukocytes >= 2,000/uL
  • Absolute neutrophil count >= 1,000/uL
  • Platelets >= 100,000/uL
  • Total bilirubin =< within 2 x upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< within 3 x upper limit of normal
  • Serum creatinine within normal institutional limits OR creatinine clearance > 30 mL/min (by Cockcroft-Gault formula)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • EXCLUSION CRITERIA FOR ARM A AND B
  • Patients who have had systemic anti-tumor therapy (such as chemotherapy, biologic modifiers or antiangiogenic therapy) within 4 weeks (6 weeks if nitrosourea or mitomycin chemotherapy) prior to study entry
  • Patients who have had external beam radiation therapy within 1 week or if the adverse events associated with radiation are not resolved to grade 1 or less prior to study entry
  • Prior therapy with sorafenib (BAY 43-9006), ZD 6474 or AMG-706
  • Patients currently receiving any other tumor-specific therapy for thyroid cancer or investigational therapy; patients receiving adjuvant hormonal therapy for a second primary (such as breast cancer or prostate cancer) are allowed to participate as far as there are no known drug interactions
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sorafenib (BAY 43-9006)
  • Patients unable to swallow sorafenib tablets (e.g. any condition that impairs patient's ability to swallow pills)
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled hypertension, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with any evidence of a bleeding diathesis
  • Patients actively receiving anticoagulation with therapeutic intent; prophylactic anticoagulation (i.e. low dose warfarin) or venous or arterial access devices is allowed provided that the prothrombin time (PT), international normalized ratio (INR) or partial thromboplastin time (PTT) are normal
  • Pregnant women or women who are breast-feeding are excluded from this study; breastfeeding should be discontinued if the mother is treated with sorafenib (BAY 43-9006)
  • Human immunodeficiency virus (HIV)-positive patients receiving combination anti-retroviral therapy
  • Patients taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin or St. John's Wort
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
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, NCI-7609, OSU 06054 / IRB 2006C0050, 2006C0050, OSU-06054, 7609, N01CM62207, P30CA016058
Study First Received: October 18, 2006
Last Updated: September 30, 2014
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on October 01, 2014