Bortezomib in Treating Patients With Metastatic Thyroid Cancer That Did Not Respond to Radioactive Iodine Therapy

Study Overview
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Brief Summary
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This phase II trial is studying how well bortezomib works in treating patients with metastatic thyroid cancer that did not respond to radioactive iodine therapy. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the efficacy of bortezomib, in terms of tumor response rate, in patients with metastatic papillary or follicular thyroid cancer unresponsive to prior radioiodine therapy. SECONDARY OBJECTIVE: I. Determine the clinical activity of this drug, in terms of progression-free survival, in patients treated with this drug. OUTLINE: This is an open-label, multicenter study. Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically.

Official Title
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A Phase II Study of Bortezomib in Metastatic Papillary Thyroid Carcinoma or Follicular Thyroid Carcinoma

Conditions
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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

Intervention / Treatment
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* Drug: Bortezomib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The Eastern Cooperative Oncology Group (ECOG) 0-2 OR Karnofsky 60-100% Platelet count >= 100,000/mm^3 Absolute neutrophil count >= 1,500/mm^3 White Blood Count (WBC) >= 3,000/mm^3 Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =< 2.5 times upper limit of normal Bilirubin normal No symptomatic congestive heart failure Creatinine normal OR creatinine clearance >= 60 mL/min No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except basal cell skin cancer or carcinoma in situ of the cervix No ongoing or active infection No psychiatric illness or social situation that would preclude study compliance No other uncontrolled illness At least 4 weeks since prior chemotherapy No more than 2 prior chemotherapy regimens At least 6 months since prior external beam radiotherapy for locoregional disease in the thyroid bed or to the cervical or upper mediastinal lymph nodes (dose =< 6,000 cGy) At least 6 months since prior radioiodine therapy No prior external radiotherapy to the measured tumor Prior thyroidectomy allowed No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No other concurrent anticancer therapy Unresponsive to prior radioiodine therapy Histologically confirmed differentiated thyroid cancer-papillary or follicular type, including, but not limited to, any of the following variants: hurthle cell (oxyphilic), insular, columnar cell, tall cell Metastatic disease At least 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan No prior radiotherapy to the only measurable lesion No radioiodine uptake in the measured metastatic tumor by radioiodine scan (Note: Must have had >= 1 radioiodine scan since the last radioiodine treatment) No known brain metastases

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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bortezomib<br>Bortezomib 1.3 mg/m^2 intravenous (IV) at over 3-5 seconds on days 1, 4, 8, and 11. Treatment repeats every 21 days for at least 4 courses. | Drug: Bortezomib<br>* Administered IV at the dose of 1.3 mg/m^2 on a twice-weekly schedule for 2 consecutive weeks on days 1, 4, 8, and 11, followed by a 10 day rest period on days 12-21 (one cycle). In the absence of clinical progression, treatment continued for a minimum of 4 treatment cycles (or 12 weeks).<br>* Other names: VELCADE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Tumor Response Rate Assessed by RECIST | Response Rate calculated as number of participants with Complete or Partial Response divided by total participants. Baseline scan and confirmatory scans obtained 6 weeks following initial documentation of objective response using Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Baseline to 12 weeks | 
| Participant Tumor Response Assessed by RECIST | Baseline scan and confirmatory scans obtained 6 weeks following initial documentation of objective response using Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): >30% decrease in sum longest diameter (LD) of target lesions, taking as reference the baseline sum LD; Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. | Baseline to 12 weeks (minimum of 4 treatment cycles (or 12 weeks)) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival Assessed by RECIST | Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | At 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hurthle cell, insular cell, columnar cell, National Thyroid Cancer Treatment Cooperative Study Group, NTCTCSG, bortezomib, velcade, metastatic differentiated thyroid carcinoma, Differentiated thyroid carcinoma, follicular epithelial thyroid cells, papillary, oxyphilic cell, tall cell