Study Of AG-013736 In Patients With 131I-Refractory Thyroid Cancer

Study Overview
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Brief Summary
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The primary purpose is to determine how effective AG-013736 is in shrinking thyroid cancer that is resistant to radioactive iodine

Detailed Description
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Additional study details: assess safety and efficacy

Official Title
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A Pivotal Phase 2 Study Of The Anti-Angiogenesis Agent AG-013736 In Patients With 131I-Refractory Metastatic Or Unresectable Locally-Advanced Thyroid Cancer

Conditions
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Thyroid Neoplasms

Intervention / Treatment
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* Drug: AG-013736


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radioiodine-refractory metastatic or unresectable locally-advanced thyroid cancer At least 1 measurable target lesion, as defined by RECIST Exclusion Criteria: Thyroid lymphoma Previous treatment with anti-angiogenesis agents No myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism within 12 months prior.

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

Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br> | Drug: AG-013736<br>* AG-013736, tablets 5 mg BID , treatment will continue until tumor progression or toxicity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Objective Response (OR) | Percentage of participants with OR based on assessment of confirmed complete response (CR) or confirmed partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST). CR: disappearance of all target/non-target lesions and no appearance of new lesions. PR: at least (>=)30 percent(%) decrease in sum of the longest dimensions (LDs) of the target lesions (taking as a reference the baseline sum), without progression of non-target lesions and no appearance of new lesions. Confirmed responses: those persist on repeat imaging study >=4 weeks after initial documentation of response. | Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS: Time in weeks from the start of study treatment to first documentation of objective disease progression or to death due to any cause, whichever occurred first. PFS was calculated as (first event date minus the date of first dose of study treatment plus 1) divided by 7. Progression is defined using RECIST, as >=20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD since start of study and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions. | Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up) | 
| Duration of Response (DR) | Time in weeks from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to any cause minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 7. DR was calculated for the subgroup of participants with a confirmed objective tumor response. | Baseline until disease progression or initiation of antitumor therapy or death due to any cause, assessed every 8 weeks up to 28 days after last dose (follow-up) | 
| Overall Survival (OS) | Time in weeks from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the participant current status was death). | Baseline to death due to any cause or at least 2 year after the first dose for the last participant | 
| Change From Baseline in MD Anderson Symptom Assessment Inventory (MDASI) Symptom Severity Score | Symptom severity score is comprised of average of 13 MDASI core items (pain, fatigue, nausea, disturbed sleep, distressed, shortness of breath, remembering things, lack of appetite, drowsy, dry mouth, sadness, vomiting, numbness or tingling). Participants were asked to rate severity of each symptom at their worst in last 24 hours; each item rated from 0 to 10, with 0 = symptom not present and 10 = as bad as you can imagine. Total average score range: 0 to 10. Lower scores indicated better outcome. | Baseline, Cycle 1 Day 15 (C1D15), C2D1, C2D15, thereafter D1 of each cycle up to 28 days after last dose (follow-up) | 
| Change From Baseline in MD Anderson Symptom Assessment Inventory (MDASI) Symptom Interference Score | Symptom interference score is comprised of average of 6 function items from MDASI core (general activity, mood, work, relations with others, walking, and enjoyment of life). Participants were asked to rate how much symptoms have interfered in last 24 hours; each item rated from 0 to 10, with 0 = did not interfere and 10 = interfered completely. Total average score range: 0 to 10. Lower scores indicated better outcome. | Baseline, Cycle 1 Day 15 (C1D15), C2D1, C2D15, thereafter D1 of each cycle up to 28 days after last dose (follow-up) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VEGFR inhibitor, tyrosine kinase inhibitor, anti-angiogenic, carcinoma, papillary, follicular, medullary, anaplastic