Efficacy and Safety Study of Sorafenib to Treat Advanced Medullary Thyroid Carcinoma

Study Overview
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Brief Summary
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The purpose of his study is to evaluate the efficacy and safety of Sorafenib versus placebo in subjects with locally advanced medullary thyroid cancer (MTC). The primary study objective is to compare the Progression-free Survival (PFS) of the Sorafenib treatment group with the placebo treatment group in patients with advanced MTC.

Official Title
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Randomized Double-blind Placebo Controlled Phase II Study to Evaluate the Efficacy and Safety of Sorafenib Treatment in Patients With Advanced (Recurrent, Persistent and/or Metastasizing) Medullary Thyroid Carcinoma

Conditions
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Medullary Thyroid Carcinoma

Intervention / Treatment
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* Drug: Sorafenib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inpatient or outpatient ≥ 18 years of age Histologically confirmed medullary thyroid carcinoma Recurrent or persistent local disease and/or distant metastases No more than one prior line of systemic therapy Best available supportive care to control (endocrine) symptoms At least one defined lesion in CT or MRI evaluable for Response Evaluation Criteria in Solid Tumors (RECIST v1.1), or at least one defined lesion in CT or MRI not evaluable by RECIST in combination with elevated tumour markers Progression within previous 12 months Hb > 8g/dl, white blood cells (WBC) >3.000 cells/mm³ (ANC > 1.500 cells/mm³), platelets > 100.000 cells/mm³, bilirubin < 2mg/dl, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN) Performance status: WHO ≤ 2; Karnofsky index ≥ 50% Sufficient renal function (creatinin <1.5 mg/dl and creatinin clearance > 30ml/min) International normalized ratio (INR) and partial thromboplastin time (PTT) < 1.5 x ULN No acute infections Staging studies (MRT or CT and Calcitonin or CEA) completed within four weeks of protocol randomisation Women of childbearing potential with negative serum pregnancy test Women and men of childbearing potential using adequate contraception Signed and dated written informed consent Exclusion Criteria: Unresolved toxicity (i.e. neurotoxicity) attributed to any prior therapy higher than National Cancer Institute-Common Toxicity Criteria for Adverse Effects (NCI-CTCAE version 4) Grade 2 (excluding cases of alopecia) Patients with history of allergic or hypersensitivity reaction to study drug or placebo or their excipients Current participation in another investigational trial Patients with significant cardiovascular disease Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy other than beta-blockers or digoxin Congenital long corrected QT interval (QTc) syndrome, history of drug induced QTc prolongation, or QTc interval unmeasurable or more than 450 ms Abnormal serum electrolytes such as potassium, magnesium and calcium Uncontrolled hypertension, despite optimal management Major surgery, open biopsy, or significant traumatic injury within 30 days prior to randomization Non-healing wound, ulcer, or bone fracture Evidence or history of bleeding diathesis or coagulopathy disorder Hemorrhage/bleeding event ≥ Grade 3 Thrombotic or embolic events including transient ischemic attacks within the past 6 months Subjects with symptomatic brain metastases or Subjects with brain metastases under corticosteroid treatment Pregnant or breast-feeding patients Patients with uncontrolled infections Known HIV infection or infection with hepatitis B or C Immunosuppression Subjects with seizure disorder requiring medication • Subjects undergoing renal dialysis Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results Any malabsorption condition

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 |
| --- | --- |
| Experimental: Sorafenib tablets<br>Oral administration of Sorafenib tablets, 400 mg bid, until disease progression or unacceptable toxicity | Drug: Sorafenib<br> <br> |
| Placebo Comparator: Placebo tablets<br>Oral administration of Placebo tablets until disease progression, afterwards continuation with Sorafenib at the discretion of the investigator | Drug: Sorafenib<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | The proportion of patients with PFS in the Sorafenib group and the Placebo group will be compared by log rank test and Kaplan-Meier plot. | from the date of randomisation until the date of radiological or biochemical progression or death. An average of 9 months is assumed. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Progression (TPP) | The average TTP in the Sorafenib group and the Placebo group will be compared. | from the date of randomisation until the date of confirmed radiological or biochemical progression. An average of 9 months is assumed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Medullary Thyroid Carcinoma, Sorafenib, Efficacy