Sorafenib in Treating Patients With Advanced Anaplastic Thyroid Cancer

Phase II Trial of BAY 43-9006 in Patients With Advanced Anaplastic Carcinoma of the Thyroid

This phase II trial is studying how well sorafenib works in treating patients with advanced anaplastic thyroid cancer. 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.

Study Overview

• Status: Terminated
• Conditions: Recurrent Thyroid Cancer; Anaplastic Thyroid Cancer
• Intervention / Treatment: Drug: sorafenib tosylate

Detailed Description

OBJECTIVES:

I. Determine whether the objective response rate is ≥ 20% in patients with advanced anaplastic thyroid cancer treated with sorafenib.

II. Determine the survival of patients treated with this drug. III. Determine the safety profile of this drug in these patients. IV. Determine the pharmacokinetic predictors of response to this drug in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for survival.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case Western Reserve University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Criteria:

• Progressive disease after prior cytotoxic chemotherapy (i.e., chemotherapy alone or combined with radiotherapy)
• No symptomatic bulky disease that would impair the airway or impede swallowing (for patients with ECOG performance status 2)
• No known brain metastases

• Measurable or evaluable disease

  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
  • Measurable disease not in a previously irradiated field
• Patients with evidence of abnormal cardiac conduction (e.g., bundle branch block or heart block) are eligible provided disease has been stable for the past 6 months

• Performance status:

  • ECOG 0-2 OR Karnofsky 50-100%
• Life expectancy more than 8 weeks
• Absolute neutrophil count >= 1,250/mm3
• Platelet count >= 100,000/mm3
• No evidence of bleeding diathesis
• Bilirubin =< 1.5 times upper limit of normal (ULN)
• PTT =< 1.5 times ULN
• Creatinine =< 1.5 times ULN
• No myocardial infarction within the past 6 months
• No New York Heart Association class III or IV cardiac disease
• No symptomatic congestive heart failure
• No unstable angina pectoris
• No uncontrolled hypertension (i.e., systolic blood pressure (BP) > 150 mm Hg OR diastolic BP > 100 mm Hg)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to swallow oral medication
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to sorafenib
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other invasive malignancy within the past 5 years except nonmelanoma skin cancer
• No other uncontrolled illness
• No more than 2 prior systemic cytotoxic chemotherapy regimens (combined modality systemic cytoxic chemotherapy is considered 1 prior cytotoxic regimen)
• At least 7 days since prior chemotherapy and recovered
• At least 7 days since prior radiotherapy and recovered
• No prior sorafenib or other inhibitors of MAP kinase signaling intermediates
• No prior cancer treatment that would preclude study participation
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No other concurrent investigational agents
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent Hypericum perforatum (St. John's wort) or rifampin
• No concurrent therapeutic anticoagulation (concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided requirements for INR and PTT are met)
• No other concurrent anticancer therapy

• Histologically confirmed anaplastic* thyroid cancer

  • Not amenable to definitive curative surgery or radiotherapy [Note: *Papillary, follicular, or other histologies that are mixed or identified in a diagnostic tissue sample are allowed provided a high-grade undifferentiated anaplastic component is present ]
• No cardiac arrhythmia
• AST and ALT =< 3.5 times ULN
• INR < 2.0

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (sorafenib tosylate); Patients receive oral sorafenib twice daily on days 1-28. Courses repeat every 28 days 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Response to Treatment Measured by RECIST Criteria	Response evaluated using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. The patient's best response depends on the achievement of measurement and confirmation criteria of Complete Response (CR), Stable Disease (SD), Partial Response (PR) or Progressive Disease (PD). Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques (CT, MRI, x-ray) or as >10 mm with spiral CT scan.	at 6 months after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival Was Measured From the Date of Outset of Treatment to the Date of Disease Progression.		27 months
Overall Survival Was Measured From the Date of Outset of Treatment to the Date of Death.		27 months
Number of Participants That Experienced Adverse Events to Characterize the Safety Profile of BAY 43-9006	The safety and toxicity profile of BAY 43-9006 as measured by toxicity grades of adverse events.	27 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Panayiotis Savvides, Case Western Reserve University

Publications and helpful links

General Publications

• Savvides P, Nagaiah G, Lavertu P, Fu P, Wright JJ, Chapman R, Wasman J, Dowlati A, Remick SC. Phase II trial of sorafenib in patients with advanced anaplastic carcinoma of the thyroid. Thyroid. 2013 May;23(5):600-4. doi: 10.1089/thy.2012.0103. Epub 2013 Apr 18.

Study record dates

Study Major Dates

• Study Start: June 1, 2005
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: August 2, 2005
• First Submitted That Met QC Criteria: August 2, 2005
• First Posted (Estimate): August 4, 2005

Study Record Updates

• Last Update Posted (Actual): January 19, 2018
• Last Update Submitted That Met QC Criteria: December 20, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Endocrine Gland Neoplasms; Head and Neck Neoplasms; Thyroid Diseases; Thyroid Neoplasms; Thyroid Carcinoma, Anaplastic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2009-00118 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U01CA062502 (U.S. NIH Grant/Contract); CASE 5304 (Other Identifier: Case Western Reserve University); CDR0000437789; 7037 (Other Identifier: CTEP)