To Compare The Effects Of Two Doses Of Vandetanib In Patients With Advanced Medullary Thyroid Cancer

Study Overview
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Brief Summary
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The purpose of this study is to give patients with medullary thyroid cancer either 300mg/day or 150mg/day vandetanib and compare how well each dose affects how their cancer responds. It will also help the investigators understand the side effects of different doses in these patients.

Detailed Description
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An International, Randomised, Double-Blind, Two-Arm Study To Evaluate The Safety And Efficacy Of Vandetanib 150 And 300mg/Day In Patients With Unresectable Locally Advanced Or Metastatic Medullary Thyroid Carcinoma With Progressive Or Symptomatic Disease

Official Title
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An International, Randomised, Double-Blind, Two-Arm Study To Evaluate The Safety And Efficacy Of Vandetanib 150 And 300mg/Day In Patients With Unresectable Locally Advanced Or Metastatic Medullary Thyroid Carcinoma With Progressive Or Symptomatic Disease

Conditions
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Thyroid Cancer

Intervention / Treatment
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* Drug: 300mg vandetanib
* Drug: 150mg vandetanib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written consent from Female or male patients aged 18 years and over. Previously confirmed histological diagnosis of unresectable, locally advanced or metastatic, hereditary or sporadic MTC Objective disease progression within the previous 14 months prior to enrolment, and/or Have one or more symptoms that the Investigator believes to be related to the patient's MTC. World Health Organisation (WHO) or Eastern Cooperative Oncology Group (ECOG) Performance status 0-2. Has measurable disease (at least one lesion, not irradiated within 12 weeks of study randomisation, with longest diameter more or equal 10mm (lymph nodes minimum more or equal 15 mm) with CT or MRI). Lesions must be amenable to accurate and repeat measurement. Exclusion Criteria: Prior treatment (major surgery, radiation therapy, chemotherapy, or other investigational drugs) received within 28 days before randomization. Abnormal liver function tests (bilirubin more than 1.5xULRR, and ALT, AST, or ALP more than 2.5xULRR or 5.0xULRR if related to liver metastases). Significant cardiac conditions or events such as reduced cardiac functions, symptomatic cardiac arrhythmia requiring treatment, congenital long QT syndrome, history of drug-induced QT prolongation, or QTcF correction unmeasurable or more than 450 ms. Abnormal electrolytes such as potassium, magnesium and calcium, or abnormal organ functions such as decreased creatinine clearance. For women only - currently pregnant or breast feeding.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 300mg vandetanib<br> | Drug: 300mg vandetanib<br>* Oral blinded tablets taken once daily. At objective disease progression or 14 months (whichever is earlier), patient may be unblinded to treatment Dosing with unblinded study treatment can continue until 24 months after patient was randomised. At any time dosing may be interrupted for up to 6 weeks due to toxicity. Dosing may restart at a reduced dose (200mg/day). Once reduced, dose increases are not permitted and dosing must stop if further toxicities occur.<br>* Other names: SAR390530;|
| Active Comparator: 150mg vandetanib<br> | Drug: 150mg vandetanib<br>* Oral blinded tablets taken once daily. At objective disease progression or 14 months (whichever is earlier), patient may be unblinded to treatment. Patients who have not dose reduced at the time of unblinding may have their dose increased to 300mg Dosing with unblinded study treatment can continue until 24 months after patient was randomised At any time dosing may be interrupted for up to 6 weeks due to toxicity. Dosing may restart at a reduced dose (100mg/day) [OR 300 reduced to 200mg/day if dose was increased at unblinding.] Once reduced, dose increases are not permitted and dosing must stop if further toxicities occur.<br>* Other names: SAR390530;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) for Vandetanib 150 and 300mg With Responses Determined by the Investigator | ORR=proportion of patients with a best response of complete or partial response as per Response Evaluation Criteria in Solid Tumors(RECIST)1.1 | Randomisation to week 60 (maximum) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Best Objective Response |  | Randomisation to week 60 (maximum) | 
| Duration of Objective Response (RECIST 1.1) by Treatment Arm |  | Randomization to Week 60 (maximum) | 
| Time to Objective Response (RECIST 1.1) by Treatment Arm |  | Randomization to Week 60 (maximum) | 
| Percentage Change From Baseline in Target Lesion Size (RECIST 1.1) by Treatment Arm |  | Randomization to Week 60 (maximum) | 
| Plasma Concentration of Vandetanib in the Bloodstream (Cmax) for Patients by Treatment Arm. |  | Week 3 to week 60 (maximum) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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medullary thyroid cancer, metastatic, thyroid cancer, carcinoma of the thyroid, receptor tyrosine kinase inhibitor, VEGFR, Unresectable locally advanced thyroid cancer