Efficacy and Tolerability of ZD6474 in Patients With Thyroid Cancer

Study Overview
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Brief Summary
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The purpose of this open label, two stage, phase II study is to evaluate the efficacy and tolerability of ZD6474 in patients with locally advanced or metastatic hereditary medullary thyroid carcinoma.

Official Title
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An Open Label, Two Stage, Phase II Study to Evaluate the Efficacy and Tolerability of ZD6474 in Patients With Locally Advanced or Metastatic Hereditary Medullary Thyroid Carcinoma.

Conditions
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Thyroid Cancer

Intervention / Treatment
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* Drug: ZD6474 (vandetanib)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or hereditary medullary thyroid cancer Signed informed consent One or more measurable lesions Exclusion Criteria: Brain metastases or spinal cord compression Specific laboratory ranges Specific heart problems Prior chemotherapy and/or radiation therapy Participation in other trials within 30 days

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 130 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: Caprelsa (vandetanib) 300 mg<br>Daily oral dose of Caprelsa (vandetanib) 300mg | Drug: ZD6474 (vandetanib)<br>* oral once daily tablet<br>* Other names: SAR390530;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate | The ORR is the number of patients that are responders ie those patients with a confirmed best objective response of complete response (CR) or partial response (PR) defined according to RECIST 1.0. | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival | Median time to progression defined according to RECIST 1.0 (months) from randomisation until objective disease progression or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | 
| Duration of Objective Response | Median duration of objective response as defined according to RECIST 1.0 from onset of response until data of objective disease progression or death from any cause in days. | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | 
| Disease Control Rate | Disease control rate was defined as the number of patients who had a best response of Complete Response (CR), or Partial Response (PR) or stable disease (SD) ≥24 weeks as defined according to RECIST 1.0. | Pre-dose and every 12 weeks up to RECIST progression as defined according to RECIST 1.0. | 
| Biochemical Response Calcitonin (CTN) | A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a confirmed best biochemical response of Complete Response or Partial (i.e. complete normalization of CTN or at least a 50% decrease in CTN from baseline). | Blood samples for analysis of CTN taken on Day 1 (every 3 hours for 24 hours), then a single sample on Day 5, weekly through the first 2 assessment periods, monthly (prior to amendment 7) and every 12 weeks (following amendments) until discontinuation | 
| Symptomatic Response | Number of participants with a reduction of frequency and improvement in consistency of stool to normal (no more than 2 solid stools daily without concomitant anti-diarrheal medication) following administration of Caprelsa (vandetanib) denoted a symptomatic CR. An improvement in stool consistency to mostly semisolid and decrease in stool frequency to 50% or greater denoted symptomatic PR. | Symptomatic diarrhea was assessed using stool frequency and consistency diaries. Baseline was established using the average of the 4 days immediately prior to first dose on Day 5. Diaries were completed every day for the first 6 months on study drug. | 
| World Health Organisation (WHO) Performance Status | Number of patients demonstrating a worsening (increase in score of one or more from baseline) in WHO PS from baseline to 24 weeks. WHO PS is scored zero (Fully active) to 4 (completely disabled) | Performance status was assessed using the WHO criteria at baseline and because SD lasting for at least 24 weeks was used in the definition of disease control (in addition to confirmed objective response), WHO PS at 24 weeks was evaluated. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caprelsa (vandetanib), ZD6474