A Study To Assess ZD6474 (ZACTIMA™) Monotherapy In Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

Study Overview
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Brief Summary
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This will be a Phase II, open label study to establish the effect of once-daily oral doses of ZD6474 100mg in subjects with locally advanced or metastatic hereditary medullary thyroid cancer in whom no standard therapeutic option is available.

Official Title
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A Phase II, Open-Label Study To Assess The Efficacy and Tolerability of ZD6474 (ZACTIMA™ ) 100 mg Monotherapy In Subjects With Locally Advanced or Metastatic Hereditary Medullary Thyroid Cancer

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: Provision of written informed consent Previously confirmed histological diagnosis of locally advanced or metastatic hereditary medullary thyroid carcinoma without standard therapeutic options Aged 18 or over and a life expectancy of more than 12 weeks Exclusion Criteria: The last dose of prior chemo/radiation received less than 4 weeks before the start of study therapy Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age, history of arrhythmia

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: 1<br> | Drug: ZD6474 (vandetanib)<br>* 100 mg once daily oral tablet<br>* Other names: Caprelsa™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | 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) as defined by RECIST criteria. The categories for best objective response are CR, PR, stable disease (SD)>= 12 weeks, progressive disease (PD) or NE. | RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | Median progression free survival (months) estimated from a Weibull model with corresponding 95% confidence intervals. Progression free survival is the time from randomisation until objective disease progression (determined by RECIST assessments) or death (by any cause in the absence of objective progression) provided death is within 3 months from the last evaluable RECIST assessment. | RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment. | 
| Disease Control Rate (DCR) | Disease control rate is defined as the number of patients who achieved disease control at 8 weeks following randomisation. Disease control at 8 weeks is defined as a best objective response of complete response (CR), partial response (PR) or stable disease (SD) >= 24 weeks | RECIST assessed at screening (up to 3 weeks prior to first dose), then every 12 weeks (± 2 weeks), from date of first dose to objective progression, up to and including discontinuation of study treatment. | 
| World Heath Organization (WHO) Performance Status | Number of patients demonstrating an improvement from baseline to 24 weeks in WHO PS. Where WHO PS is the standard scale with patients scored (0 healthy - 5 dead) based on their physical capabilities | WHO PS assessed at screening (up to 3 weeks prior to first dose), baseline and then every 12 weeks (± 2 weeks), up to and including discontinuation of study treatment. | 
| Symptomatic Response | Symptomatic response will be defined as at least a 50% decrease in the stool frequency (represented by a persistent decrease in stool frequency over 4 weeks), taking as reference the baseline (mean) level. | Symptomatic diarrhea was assessed using stool frequency diaries. Baseline was established using the average of the 4 days immediately prior to first dose, then weekly until discontinuation of study treatment. | 
| 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 best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for PR or CR were first met. | Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation Time point(s) at which outcome measure was assessed. (Limit: 255 characters) | 
| Biochemical Response Carcinoembryonic Antigen CEA) | A patient's best biochemical response was calculated from assessments performed at baseline and during treatment. Responders were those patients with a best biochemical response of CR or PR, confirmed by repeat assessments, which were to be performed no less than 4 weeks after the criteria for Partial Response (PR) or Complete Response (CR) were first met. | Blood samples for analysis of CTN were taken at screening (0, 1, 4, and 8 hours to determine the baseline CTN/CEA level) then every 4 weeks until discontinuation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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medullary thyroid cancer, MTC, hereditary medullary thyroid cancer, thyroid cancer