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

• ClinicalTrials.gov Identifier: NCT00095693
• Recruitment Status: Terminated
• First Posted: November 8, 2004
• Last Update Posted: January 16, 2014
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

Study Description

Brief Summary:

Phase II trial to study the effectiveness of sorafenib tosylate in treating patients who have locally advanced, metastatic, or locally recurrent thyroid cancer. Sorafenib tosylate may stop the growth of tumor cells by blocking the enzymes necessary for their growth and by stopping blood flow to the tumor.

Condition or disease	Intervention/treatment	Phase
Anaplastic Thyroid Cancer; Insular Thyroid Cancer; Recurrent Thyroid Cancer; Stage III Follicular Thyroid Cancer; Stage III Papillary Thyroid Cancer; Stage IV Follicular Thyroid Cancer; Stage IV Papillary Thyroid Cancer	Drug: sorafenib tosylate; Other: laboratory biomarker analysis; Other: pharmacological study; Radiation: fludeoxyglucose F 18; Procedure: positron emission tomography; Procedure: dynamic contrast-enhanced magnetic resonance imaging	Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Determine objective response rate in patients with locally advanced, metastatic, or locally recurrent differentiated thyroid cancer treated with sorafenib (BAY 43-9006).

SECONDARY OBJECTIVES:

I. Determine the toxicity of this drug in these patients. II. Correlate thyroglobulin levels with tumor response in patients treated with this drug.

III. Correlate fludeoxyglucose F 18 positron emission tomography results with tumor response in patients treated with this drug.

IV. Correlate tumor permeability and vascularity, as determined by dynamic contrast-enhanced MRI, with tumor response in patients treated with this drug.

V. Determine the pharmacodynamics of this drug in these patients. VI. Correlate the presence and type of B-raf, N-ras, or RET/PTC gene mutations with clinical response in patients treated with this drug.

VII. Correlate the degree of Ras-MAPK signaling inhibition and vascular endothelial growth factor expression with clinical response in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (papillary thyroid cancer that is chemo-naïve vs all others).

Patients receive oral sorafenib tosylate twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving complete remission (CR) receive 8 additional weeks of therapy beyond CR.

Patients are followed within 2-4 weeks after completion of study treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Study of BAY 43-9006 in Patients With Metastatic Thyroid Carcinoma
• Study Start Date: October 2004
• Actual Primary Completion Date: August 2005
• Actual Study Completion Date: December 2011

Arms and Interventions

Arm

Intervention/treatment

Experimental: Treatment (sorafenib tosylate); Patients receive oral sorafenib tosylate twice daily for up to 6 months in the absence of disease progression or unacceptable toxicity. Patients achieving CR receive 8 additional weeks of therapy beyond CR.

Drug: sorafenib tosylate; Given PO; Other Names: BAY 43-9006; BAY 43-9006 Tosylate Salt; BAY 54-9085; Nexavar; SFN; Other: laboratory biomarker analysis; Correlative studies; Other: pharmacological study; Correlative studies; Other Name: pharmacological studies; Radiation: fludeoxyglucose F 18; Correlative studies; Other Names: 18FDG; FDG; Procedure: positron emission tomography; Correlative studies; Other Names: FDG-PET; PET; PET scan; tomography, emission computed; Procedure: dynamic contrast-enhanced magnetic resonance imaging; Correlative studies; Other Name: DCE-MRI

Outcome Measures

Primary Outcome Measures :

1. Objective response rate [ Time Frame: Up to 4 weeks ]
   The 95% confidence intervals should be provided.

Secondary Outcome Measures :

1. Incidence of toxicity [ Time Frame: Up to 4 weeks ]

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically confirmed diagnosis of 1 of the following:

  • Papillary thyroid cancer (stratum I)

  • Papillary, follicular, Hurthle cell, insular, or anaplastic thyroid cancer (stratum II)

    • Mixed histology, poorly differentiated, or tall-cell variants allowed
• Metastatic, locally advanced, or locally recurrent disease

• At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan

  • The following are considered non-measurable disease:

    • Tumors in a previously irradiated area
    • Bone lesions
    • Leptomeningeal disease
    • Ascites
    • Pleural/pericardial effusion
    • Lymphangitis cutis/pulmonis
    • Abdominal masses not confirmed and followed by imaging techniques
    • Cystic lesions
• Archival tumor tissue block OR material collected before study entry available (stratum I)
• Biopsy-accessible disease (stratum I)
• Performance status - ECOG 0-1
• At least 6 months
• WBC >= 3,000/mm^3
• Absolute neutrophil count >= 1,500/mm^3
• Platelet count >= 100,000/mm^3
• No bleeding diathesis
• Bilirubin =< 1.5 times upper limit of normal (ULN)
• AST and ALT =< 1.5 times ULN
• Creatinine =< 1.5 times ULN
• No uncontrolled hypertension
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Willing to undergo 2 tumor biopsies during study participation (stratum I)
• No history of allergic reaction attributed to compounds of similar chemical or biologic composition to sorafenib
• No ongoing or active infection
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No other concurrent malignancy except nonmetastatic nonmelanoma skin cancer or carcinoma in situ of the cervix

• No prior systemic chemotherapy for thyroid cancer (stratum I)

  • Prior systemic chemotherapy used to treat a second primary cancer with curative intent allowed provided the primary cancer was treated more than 5 years before study entry
• No more than 3 prior systemic chemotherapy regimens for thyroid cancer (stratum II)
• More than 6 weeks since prior systemic chemotherapy (stratum II)
• No prior external beam radiotherapy to the sole site of measurable disease (except for patients with anaplastic thyroid cancer)
• More than 6 weeks since prior external beam radiotherapy
• More than 24 weeks since prior iodine I 131
• Recovered from all prior therapy
• No prior sorafenib
• More than 6 weeks since prior investigational tumor-specific therapy
• Concurrent oral or IV bisphosphonates for bony metastases allowed at the discretion of the investigator
• No other concurrent tumor-specific or investigational therapy
• No concurrent combination antiretroviral therapy for HIV-positive patients

• No concurrent therapeutic anticoagulation

  • Concurrent prophylactic anticoagulation (e.g., low-dose warfarin) for venous or arterial access devices allowed provided PT, INR, or PTT are normal

Contacts and Locations

Locations

United States, Ohio

Ohio State University Medical Center

Columbus, Ohio, United States, 43210

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

• Principal Investigator: Manisha Shah; Ohio State University

More Information

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00095693
• Other Study ID Numbers: NCI-2012-01457; NCI-2012-01457 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); OSU-0441; CDR0000393968; NCI-6608; OSU-2004C0068; OSU 0441 ( Other Identifier: Ohio State University Medical Center ); 6608 ( Other Identifier: CTEP ); N01CM62207 ( U.S. NIH Grant/Contract ); P30CA016058 ( U.S. NIH Grant/Contract ); N01CM62206 ( U.S. NIH Grant/Contract ); U01CA076576 ( U.S. NIH Grant/Contract )
• First Posted: November 8, 2004
• Last Update Posted: January 16, 2014
• Last Verified: January 2014

Additional relevant MeSH terms:

Thyroid Neoplasms; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Adenocarcinoma, Follicular; Thyroid Diseases; Endocrine System Diseases; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Adenocarcinoma, Papillary; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Sorafenib; Fluorodeoxyglucose F18; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals