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

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

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.

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