Overview

This trial is active, not recruiting.

Conditions multiple endocrine neoplasia, recurrent thyroid gland carcinoma, thyroid gland medullary carcinoma
Treatments laboratory biomarker analysis, pharmacological study, sorafenib tosylate
Phase phase 2
Targets RAF, FLT-3, KIT, PDGF, VEGF
Sponsor National Cancer Institute (NCI)
Start date October 2006
End date January 2017
Trial size 50 participants
Trial identifier NCT00390325, 2006C0050, 7609, CDR0000507441, N01CM62207, NCI-2009-00196, NCI-7609, NCT01645631, OSU 06054 / IRB 2006C0050, OSU-06054, P30CA016058

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Patients receive sorafenib tosylate PO BID on days 1-56. Treatment repeats every 8 weeks in the absence of disease progression or unacceptable toxicity.
laboratory biomarker analysis
Correlative studies
pharmacological study
Correlative studies
sorafenib tosylate BAY 43-9006 Tosylate
Given orally

Primary Outcomes

Measure
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

Secondary Outcomes

Measure
Calcitonin levels
time frame: Up to 4 weeks after last dose of sorafenib tosylate
CEA levels
time frame: Up to 4 weeks after last dose of sorafenib tosylate
DCE-MRI data
time frame: Up to 4 weeks after last dose of sorafenib tosylate
Degree of Ras-MAPK signaling inhibition in the tumor
time frame: Up to 4 weeks after last dose of sorafenib tosylate
Degree of VEGF expression in the tumor
time frame: Up to 4 weeks after last dose of sorafenib tosylate
Fludeoxyglucose F-18 PET data
time frame: Up to 4 weeks after last dose of sorafenib tosylate
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
RET gene defects in the tumor
time frame: Baseline
Selected polymorphisms of genes influencing sorafenib tosylate metabolism and/or resistance genes that may predict response or toxicity
time frame: Baseline

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase II Study of Sorafenib (BAY 43-9006) in Patients With Metastatic Medullary Thyroid Carcinoma
Principal investigator Manisha Shah
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.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).