Advanced or metastatic papillary or follicular Thyroid Carcinoma MedDRA version: 9.1 Level: LLT Classification code 10001205 Term: Adenocarcinoma thyroid
Conditions
Sponsors
AstraZeneca SAS
Eligibility
Sex/Gender
All
Inclusion criteria
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 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=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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. Serum creatinine >1.5 x ULRR or creatinine clearance 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 y
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate an improvement in progression free survival (PFS) with ZACTIMA™ (ZD6474) 300 mg as compared to Placebo in subjects with advanced or metastatic papillary or follicular Thyroid Carcinoma failing or unsuitable for Radioiodine therapy;Primary end point(s): Progression Free Survival;Secondary Objective: 1. To demonstrate an improvement in Disease Control Rate (DCR) [Complete Response (CR) + Partial Response (PR) + Stable disease (SD) at 6 months] with ZACTIMA™ (ZD6474) 300 mg as compared to placebo according to the RECIST (Therasse et al, 2000). 2. To quantify the improvement in Objective Response Rate (ORR) (CR+PR) with ZACTIMA™ (ZD6474) 300 mg as compared to placebo according to the RECIST. 3. To demonstrate an improvement in the Overall Survival (OS) with ZACTIMA™ (ZD6474) as compared to placebo. 4. To determine the safety and tolerability of ZACTIMA™ (ZD6474) 300 mg in subjects with advanced or metastatic papillary or follicular Thyroid Carcinoma failing or unsuitable for Radioiodine therapy. | — |
Countries
Denmark, France, Portugal, Spain, Sweden
Outcome results
None listed