Ensayo Clínico fase II aleatorizado, doble ciego, controlado con placebo, multicéntrico, para evaluar la eficacia y seguridad de ZACTIMA® en pacientes con Carcinoma papilar o folicular de Tiroides localmente avanzado o metastático que han fracasado al tratamiento con yodo radioactivo o que no son candidatos a recibirloA Randomized, Double Blind, placebo-controlled Phase II, Multi-Centre Study to Assess the Efficacy and Safety of Zactima™ in Patients with advanced or metastatic papillary or follicular Thyroid Carcinoma failing or unsuitable for Radioiodine therapy

Conditions: Carcinoma papilar o folicular de tiroides localmente avanzado o metastásicoAdvanced or metastatic papillary or follicular Thyroid Carcinoma
MedDRA version: 9.1Level: LLTClassification code 10001205Term: Adenocarcinoma thyroid

Registration Number: EUCTR2007-001890-27-ES

Lead Sponsor: AstraZeneca AB

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 135

Inclusion Criteria

1.Provision of written informed consent prior to any study-related procedures.
2.Female or male aged 18 years and over.
3.Previously confirmed histological diagnosis of locally advanced or metastatic papillary or follicular thyroid carcinoma, without anaplastic component. Tumor sample available for centralized exploratory analysis.
4.Presence of one or more measurable lesions at least 1 cm in the longest diameter by spiral CT scan or 2 cm with conventional techniques.
5.Life expectancy of 12 weeks or longer.
6.WHO Performance status 0-2.
7.Able to swallow study medication.
8.Progressive disease following RAI131 or patient unsuitable for RAI131 after surgery.
9.Serum TSH<0.5mU/L.
10.Negative pregnancy test for female subjects of childbearing potential.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1.Brain metastases or spinal cord compression, unless treated at least 4 weeks before first dose and stable without steroid treatment for 10 days.
2.Major surgery within 4 weeks before randomization.
3.Prior chemotherapy within the last 4 weeks prior to randomization.
4.RAI131 therapy within 3 months in patients with radioiodine uptake.
5.Radiation therapy within the last 4 weeks prior to randomization (with the exception of palliative radiotherapy).
6.Serum bilirubin >1.5 x the upper limit of reference range (ULRR).
7.Creatinine clearance < 30 ml/min (calculated by Cockcroft-Gault formula).
8.Potassium <4.0 mmol/L despite supplementation; or above the CTCAE grade 1 upper limit.
9.Magnesium below the normal range despite supplementation or above the CTCAE grade 1 upper limit.
10.Serum calcium above the CTCAE grade 1 upper limit.
11.In cases where the serum calcium is below the normal range:
-The calcium adjusted for albumin is to be obtained and substituted for the measured serum value. Exclusion is to then be based on the calcium adjusted for albumin values decreasing below the normal limit. Corrected calcium = Ca + 0.8 X (4-serum albumin).
12.Alanine aminotransferase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) greater than 2.5 × ULRR, or greater than 5.0 × ULRR if judged by the investigator to be related to liver metastases.
13.Clinically significant cardiovascular event (eg myocardial infarction), superior vena cava [SVC] syndrome, New York Heart Association [NYHA] classification of heart failure =II within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
14.History of arrhythmia (multifocal premature ventricular contractions [PVCs], bigeminy, trigeminy, ventricular tachycardia or uncontrolled atrial fibrillation), which is symptomatic or requires treatment (CTCAE grade 3), , or asymptomatic sustained ventricular tachycardia. Subjects with atrial fibrillation controlled by medication are permitted.
15.Congenital long QT syndrome or 1st degree relative with unexplained sudden death under 40 years of age.
16.QT prolongation with other medications that required discontinuation of that medication.
17.Presence of left bundle branch block (LBBB).
18.QTc with Bazett’s correction unmeasurable or =480 msec on screening ECG (Note: If a subject has QTc interval =480 msec on screening ECG, the screen ECG may be repeated 2 times [at least 24 hours apart]. The average QTc from the three screening ECGs must be <480 msec in order for the subject to be eligible for the study). Patients who are receiving a drug that has a risk of QTc prolongation (see Appendix E for list of medications) are excluded if QTc is = 460 msec.
19.Hypertension not controlled by medical therapy (systolic BP greater than 160 millimeter of mercury [mmHg] or diastolic blood pressure greater than 100 mmHg).
20.Any concomitant medications that may cause QTc prolongation or induce Torsades de Pointes (see Appendix E for the lists of medications in Table 1 & Table 2) or induce CYP3A4 function.
21.Currently active diarrhea that may affect the ability of the patient to absorb the ZACTIMA or tolerate diarrhea.
22.Previous or current malignancies of other histologies within the last 5 years, with the exception of in situ carcinoma of the cervix, and adequately treated basal cell or squamous cell carcinoma of the skin.
23.Any unresolved chron