Advanced (recurrent, persistent and/or metastasizing) medullary thyroid carcinoma
Conditions
Interventions
Trade Name: Nexavar
Product Name: Nexavar
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SORAFENIB TOSILATE
CAS Number: 475207-59-1
Concentration unit: mg milligram(s)
Concentration type
Sponsors
EANM Forschungs GmbH / EANM Research Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patient must be = 18 years of age when signing the informed consent form • Histologically confirmed medullary thyroid carcinoma (C-cell thyroid carcinoma) • Recurrent or persistent local disease and/or distant metastases not suitable for local curative treatment (surgery or radiation therapy) assessed by Investigator • No more than one prior line of systemic therapy (including no more than 1 prior line with a targeted drug, e.g. kinase inhibitor) • Best available supportive care to control (endocrine) symptoms according to current standards established for at least 8 weeks before study entry • At least one defined lesion in CT or MRI evaluable for RECIST (v1.1), no older than 42 days from planned treatment start, or at least one defined lesion in CT or MRI not evaluable by RECIST in combination with elevated tumour markers with minimum initial levels of 150 pg/ml for calcitonin or 5 x UILN for CEA (e.g., in case of bone metastases) • Progression within previous 12 months (according to RECIST 1.1 criteria or tumour marker progression (calcitonin or CEA referred to normal Reference Ranges from Site Lab) can be used as a basis for the assessment of disease progression); tumour marker doubling time must be no longer than 12 months (30) and a minimum initial level of 150 pg/ml for calcitonin or 5 x UILN for CEA, respectively, need to be present. The tumour marker doubling time should be estimated using the calculator at the ATA-website: http://www.thyroid.org/professionals/calculators/CDTC.php • Hb > 8g/dl, WBC >3.000 cells/mm³ (ANC > 1.500 cells/mm³), platelets > 100.000 cells/mm³, bilirubin 30ml/min • PT-INR and PTT =65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: • Unresolved toxicity (i.e. neurotoxicity) attributed to any prior therapy higher than 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 or with a history of allergic reactions attributed to compounds with similar composition to any of the study drug or placebo. • Current participation in another investigational trial • Patients with significant cardiovascular disease, such as myocardial infarction 150 mm Hg or diastolic pressure > 90 mm Hg, 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 within 3 months prior to first dose of study drug • 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. Previous or concurrent cancer that is distinct in primary site or histology from thyroid cancer within 5 years prior to randomization EXCEPT cervical cancer in situ, treated basal cell carcinoma and superficial bladder tumours [Ta (Non invasive tumour), Tis (Carcinoma in situ) and T1 (Tumour invades lamina propria)] • Pregnant or breast-feeding patients • Patients with uncontrolled infections • Known human immunodeficiency virus (HIV) infection or infection with hepatitis B or C • Immunosuppression • Subjects with seizure disorder requiring medication (such as steroids or anti¬epileptics) • 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 • Any condition that is unstable or could jeopardize the safety of the subject and their compliance in the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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;Secondary Objective: • Time To Progression (TTP) • Disease Control Rate (DCR) • Overall Response Rate (ORR) = Complete Response Rate (CR rate) + Partial Response Rate (PR rate) • Response Duration • Overall Survival (OS) • PFS after cross-over (only descriptive analysis) • TTP after cross-over • DCR after cross-over • Overall Response Rate (ORR = CR rate + PR rate) after cross-over • Safety • Quality of Life (QoL) as assessed by Patient-reported Outcome (PRO);Primary end point(s): Progression-free survival (PFS) measured as time from randomization to disease progression or death based on RECIST v1.1 evaluation or based on Tumour marker progress (CEA or calcitonin) in the first section of the study before cross-over (for the former placebo group) will be used as primary efficacy variable. The Sorafenib group and the placebo group will be compared by log rank test and Kaplan-Meier plot. The potential influence of important prognostic factors on PFS (e.g. hereditary or spontaneous MTC, pretreatment with tyrosine kinase inhibitors or other targeted drugs) will be evaluated in an exploratory fashion using a Cox regression analysis.;Timepoint(s) of evaluation of this end point: Progression free survival will be evaluated when the data are mature, i.e. when 69 PFS events have been reached. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy variables are: • Time To Progression (TTP) • DCR (CR + PR + SD rate) in first period of the study before cross-over • Overall Response Rate (ORR = CR rate + PR rate) in first period • Response duration in first period • Overall Survival (OS) • PFS after cross-over (only descriptive analysis) • TTP after cross-over • DCR after cross-over • Overall Response Rate (ORR = CR rate + PR rate) after cross-over • Patient reported outcomes (PROs), defined as health-related quality of life using the self administered FACT-G or EQ-5D by treatment group and period Secondary safety variables are: Type, severity (graded by the National Cancer Institute, Common Terminology Criteria for Adverse Events [CTCAE] Version 4.03), seriousness and relatedness of adverse events by treatment group and period, primarily based on • Clinical assessment • Laboratory values • Vital signs ;Timepoint(s) of evaluation of this end point: At end of trial. | — |
Countries
Austria, Germany
Contacts
Public ContactDipl.-Med. Ingo Weigmann
ABX-CRO advanced pharmaceutical services Forschungsgesellschaft m.b.H
Outcome results
None listed