Celecoxib in Treating Patients With Progressive Metastatic Differentiated Thyroid Cancer

Study Overview
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Brief Summary
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RATIONALE: Celecoxib may stop the growth of thyroid cancer by stopping blood flow to the tumor and by blocking the enzymes necessary for tumor cell growth. PURPOSE: Phase II trial to study the effectiveness of celecoxib in treating patients who have progressive metastatic differentiated thyroid cancer.

Detailed Description
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OBJECTIVES: Determine the efficacy of celecoxib, in terms of progression-free survival, in patients with progressive metastatic differentiated thyroid carcinoma. Correlate cyclooxygenase (COX)-2 protein expression in tumor biopsies by immunohistochemistry with clinical response in patients treated with this drug. OUTLINE: Patients receive oral celecoxib twice daily beginning on day 1. Treatment continues for 1 year in the absence of disease progression or unacceptable toxicity. Patients who achieve a complete response (CR) receive 3 additional months of therapy beyond documentation of CR. Patients are followed at 4-8 weeks. PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study within approximately 6 months.

Official Title
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Phase II Study Of Celecoxib In Metastatic Differentiated Thyroid Carcinoma

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: celecoxib


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed thyroid carcinoma, including 1 of the following subtypes: Papillary Follicular Hurthle cell Insular Assessable disease, defined by at least 1 of the following: Metastatic (including neck lymph nodes) measurable disease At least 20 mm by conventional techniques or at least 10 mm by spiral CT scan The following are not considered measurable disease: Leptomeningeal disease Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Abdominal masses that are not confirmed and followed by imaging techniques Cystic lesions Tumor lesions within a previously irradiated area Elevated serum thyroglobulin levels indicating the presence of metastatic disease Must have negative thyroglobulin antibodies Must have progressive disease within the past year, defined by at least 1 of the following: At least 20% increase in serum thyroglobulin levels At least 20% increase in the sum of the longest diameter of measurable lesions Appearance of at least 1 new lesion Failed or ineligible for standard therapy with iodine I 131 and/or surgery PATIENT CHARACTERISTICS: Age 18 and over Performance status ECOG 0-2 Life expectancy At least 1 year Hematopoietic Absolute neutrophil count at least 1,000/mm^3 Platelet count at least 75,000/mm^3 Hepatic Bilirubin no greater than 2.0 mg/dL AST/ALT no greater than 2 times upper limit of normal Renal Creatinine no greater than 2.0 mg/dL Cardiovascular No symptomatic congestive heart failure No unstable angina pectoris No uncontrolled cardiac arrhythmia Gastrointestinal No prior symptomatic or complicated peptic ulcer disease by endoscopy within the past 6 months, defined by any of the following conditions: Active gastric or duodenal ulcer Gastric or duodenal perforation Upper gastrointestinal bleeding Other Not pregnant or nursing Negative pregnancy test No prior allergic reaction to celecoxib or sulfonamides No prior urticaria, asthma, or allergic reaction to aspirin or other nonsteroidal anti-inflammatory agents No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled concurrent illness that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy Not specified Chemotherapy More than 1 month since prior systemic chemotherapy Endocrine therapy Not specified Radiotherapy See Disease Characteristics More than 3 months since prior external beam radiotherapy (unless an indicator lesion is outside the radiation field) More than 6 months since prior iodine I 131 therapy Surgery See Disease Characteristics More than 1 month since prior surgery Other More than 2 weeks since prior conventional doses of celecoxib or rofecoxib for osteoarthritis, rheumatoid arthritis, or dysmenorrhea No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No concurrent chronic (more than 1 week of therapy) fluconazole therapy Concurrent oral or IV bisphosphonates for bony metastases are allowed Concurrent low-dose aspirin (no greater than 325 mg/day) for cardiovascular disease is allowed

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: celecoxib|Treatment will be administered on an outpatient basis. Oral celecoxib will be given at the dose of 400 mg BID for total of 12 months. Patients will be advised to take this medication with food to improve absorption.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Examine efficacy of celecoxib in patients with progressive metastatic differentiated thyroid carcinoma by assessing progression free survival. |  | up to 12 months following treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantifying gene expression and protein levels of angiogenic markers[vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and tumor necrosis factor (TNF)-α] in peripheral blood mononuclear cells (PBMCs) from pre-,during- |  | pre-study, every eight weeks and off study | 
| Quantifying gene expression and protein levels of cytokines [interleukin (IL)-10, IL-12, IL-6 and interferon (IFN)-γ] in peripheral blood mononuclear cells from pre-,during-, and post-treatment blood samples. |  |  | 
| Evaluate cyclooxygenase (COX)-2 protein expression by immunohistochemistry in tumor biopsies to correlate with clinical response. |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insular thyroid cancer, recurrent thyroid cancer, stage II follicular thyroid cancer, stage II papillary thyroid cancer, stage IV follicular thyroid cancer, stage IV papillary thyroid cancer