An Efficacy Study Comparing ZD6474 to Placebo in Medullary Thyroid Cancer

Study Overview
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Brief Summary
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The purpose of this study is to learn how hereditary or sporadic medullary thyroid cancer patients, treated with ZD6474, react to the drug, what happens to ZD6474 in the human body, about the side effects of ZD6474, and if ZD6474 can decrease or prevent the growth of tumors.

Official Title
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An International, Phase III, Randomized, Double-Blinded, Placebo-Controlled, Multi-Center Study to Assess the Efficacy of ZD6474 (ZACTIMATM) Versus Placebo in Subjects With Unresectable Locally Advanced or Metastatic 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: Confirmed diagnosis of unresectable, locally advanced or metastatic hereditary or sporadic Medullary Thyroid Cancer. Presence of measurable tumor Able to swallow medication Exclusion Criteria: Major surgery within 4 weeks before randomization Last dose of prior chemotherapy received less than 4 weeks prior to randomization Radiation therapy within the last 4 weeks prior to randomization(with exception of palliative radiotherapy) Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days Significant cardiac events Previous ZD6474 treatment

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br>Placebo vandetanib | |
| Experimental: 2<br>Vandetanib | Drug: ZD6474 (Vandetanib)<br>* once daily oral tablet<br>* Other names: SAR390530;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival(PFS) | Median time to progression (months) 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. Values here are estimated (from a Weibull model) as the medians were not met. | RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent. | 

Secondary 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 assessments performed at screening (within 3 weeks before randomisation), then every 12 weeks. For patients with objective response of CR or PR, an additional confirmatory scan was performed ≥4 weeks following the date of first response. | 
| 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) >= 12 weeks | RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent | 
| Duration of Response (DoR) | Response is defined as a confirmed best objective response of CR or PR. Duration of response is defined as time from the date of first documented response until date of documented progression or death in the absence of disease progression (provided death is within 3 months of last RECIST assessment). Values are estimated as the medians weren't met | RECIST tumour assessments were performed at screening (within 3 weeks before date of randomisation), then once every 12 weeks up to and including discontinuation of blinded study treatment, unless patients had withdrawn consent | 
| Overall Survival (OS) | As data was immature at data cut off, number of death events is quoted | Number of deaths since randomisation | 
| Biochemical Response Calcitonin (CTN) | Best biochemical response was calculated from assessments 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. CR and PR being defined according to level of CTN. | Blood samples Blood samples for analysis of CTN were taken at screening baseline (average of 0, 1, 4 and 8 hours), then every 4 weeks until discontinuation and 60 day follow up | 
| Biochemical Response Carcinoembryonic Antigen (CEA) | Best biochemical response was calculated from assessments 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. CR and PR being defined according to level of CEA. | Blood samples for analysis of CEA were taken at screening baseline (average of 0, 1, 4 and 8 hours), then every 4 weeks until discontinuation and 60 day follow up | 
| Time to Worsening of Pain (TWP) | TWP was derived using the worst pain score from brief pain inventory (BPI) and patient reported opioid analgesic use. BPI uses 0 to 10 numeric rating scales asking subjects to rate their pain. | During the last week of the screening period (Day -7 to Day 0), the brief pain inventory (BPI) and opioid analgesic use were self-reported once a day for 4 days to establish baseline, then every week during blinded study treatment, up to discontinuation. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ZD6474, MTC, Hereditary Medullary Thyroid Cancer, Sporadic Medullary Thyroid Cancer, Medullary Thyroid Cancer