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

NCT ID: NCT00390325

Last Updated: 2024-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-03
• Study Completion Date: 2022-12-22

Brief Summary

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.

Detailed Description

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.

Conditions

Hereditary Thyroid Gland Medullary Carcinoma; Locally Advanced Thyroid Gland Medullary Carcinoma; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Recurrent Thyroid Gland Medullary Carcinoma; Sporadic Thyroid Gland Medullary Carcinoma; Stage III Thyroid Gland Medullary Carcinoma AJCC v7; Stage IV Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVA Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVB Thyroid Gland Medullary Carcinoma AJCC v7; Stage IVC Thyroid Gland Medullary Carcinoma AJCC v7

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (sorafenib tosylate)

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

Group Type: EXPERIMENTAL

Sorafenib Tosylate

Intervention Type: DRUG

Given PO

Interventions

Sorafenib Tosylate

Given PO

Intervention Type: DRUG

Other Intervention Names

BAY 43-9006 Tosylate; BAY 54-9085; Nexavar; sorafenib

Eligibility 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 since these agents may have anti-farnesyl transferase activity and may have some therapeutic effect in combination with sorafenib
• Life expectancy must be >= six months
• Patients must have an Eastern Cooperative Oncology Group performance status 0-2
• Leukocytes >= 2,000/uL (10 days prior to patient enrollment)
• Absolute neutrophil count >= 1,000/uL (10 days prior to patient enrollment)
• Platelets >= 100,000/uL (10 days prior to patient enrollment)
• Total bilirubin =< within 2 x upper limit of normal (10 days prior to patient enrollment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< within 3 x upper limit of normal (10 days prior to patient enrollment)
• Serum creatinine within normal institutional limits OR creatinine clearance > 30 mL/min (by Cockcroft-Gault formula) (10 days prior to patient enrollment)
• The effects of sorafenib (BAY 43-9006) on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because kinase inhibitors are known to be teratogenic, 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, for the duration of study participation, and for at least 30 days after completion of therapy; 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

• 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 because sorafenib (BAY 43-9006) is an investigational agent and teratogenicity has not been evaluated yet; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with sorafenib (BAY 43-9006), 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 because of possible pharmacokinetic interactions with sorafenib (BAY 43-9006); patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy
• Patients taking the cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin or St. John's wort due to potential drug interactions with sorafenib

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bhavana Konda

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Duke University Medical Center

Durham, North Carolina, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2009-00196

Identifier Type: REGISTRY

Identifier Source: secondary_id

2006C0050

Identifier Type: -

Identifier Source: secondary_id

NCI-7609

Identifier Type: -

Identifier Source: secondary_id

CDR0000507441

Identifier Type: -

Identifier Source: secondary_id

OSU 06054 / IRB 2006C0050

Identifier Type: -

Identifier Source: secondary_id

7609

Identifier Type: OTHER

Identifier Source: secondary_id

7609

Identifier Type: OTHER

Identifier Source: secondary_id

N01CM00070

Identifier Type: NIH

Identifier Source: secondary_id

View Link

N01CM62207

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA016058

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2009-00196

Identifier Type: -

Identifier Source: org_study_id

NCT01645631

Identifier Type: -

Identifier Source: nct_alias