A RANDOMIZED PHASE II TRIAL TO EVALUATE THE EFFICACY AND SAFETY OF VANDETANIB (ZD6474, ZACTIMATM) VERSUS VINORELBINE IN PATIENTS WITH INOPERABLE OR RELAPSED MALIGNANT MESOTHELIOMA

• Conditions: Malignant mesothelioma

• Registration Number: EUCTR2007-003633-16-DE
• Lead Sponsor: AstraZeneca AB

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-07-28
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. Provision of informed consent
2. Female and male aged 18 years and over
3. Negative pregnancy test for women of childbearing potential
4. Histologically or cytologically confirmed diagnosis of mesothelioma in an unresectable or relapsed stage
5. Progression after or Resistance to or intolerability of first line chemotherapy
6. Measurable disease (RECIST criteria)
7. ECOG performance status < 2
8. Adequate bone marrow reserve: white blood cells >3.5 x 109/l, neutrophils >1500/mL; platelets >100 x 109/l, and haemoglobin >9 g/dl.
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. Laboratory results:
- Serum bilirubin >1.5x the upper limit of reference range (ULRR)
- Serum creatinine >1.5 x ULRR or creatinine clearance < 50 mL/minute (calculated by Cockcroft-Gault formula.)
- Potassium <4.0 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation.
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 × ULRR or alkaline phosphatase (ALP) >2.5 x ULRR, or > 5x ULRR if judged by the investigator to be related to liver metastases
2. Last dose of prior chemotherapy received less than 4 weeks before the start of study therapy
3. Previous treatment with other tyrosine-kinase (TK) inhibitors.
4. Previous treatment with vinorelbine.
5. More than 1 previous anticancer therapy for the treatment of mesothelioma.
6. Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
7. Significant cardiovascular event (e.g. myocardial infarction, superior vena cava (SVC) syndrome, New York Heart Association (NYHA) classification of heart disease >2) within 3 months before entry, or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
8. 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. Atrial fibrillation, controlled on medication is not excluded.
9. Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
10. Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age.
11. Presence of left bundle branch block (LBBB)
12. QTc with Bazett’s correction that is unmeasurable, or =480 msec on screening ECG. If a patient has QTc =480 msec on screening ECG, the screening ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be <480 msec in order for the patient to be eligible for the study. Patients who are receiving a drug that has a risk of QTc prolongation (see Appendix D, Table 2) are excluded if QTc is = 460 msec.
13. Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes (see Appendix D) or induce CYP3A4 function (refer to section 3.7). Drugs listed in Appendix D, Table 2, which in the investigator’s opinion cannot be discontinued, are allowed. If a patient is receiving one of the medications in this group prior to study entry, and it cannot be discontinued before study entry, then the screening QTc must be <460msec.
14. Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
15. Currently active diarrhea that may affect the ability of the patient to absorb the vandetanib or tolerate chemotherapy.
16. Brain metastases or spinal cord compression, unless irradiated at least 4 weeks before first dose and stable without steroid treatment for > 1 week
17. Women who are currently pregnant or breast-feeding.
18. Previous or current malignancies of other histologies within the last 5 years, with the exception of c

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified