| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the efficacy of oral vandetanib 300 mg once daily compared with vinorelbine administrated intravenously weekly in patients with inoperable or relapsed malignant mesothelioma by estimating the overall disease control rate (DCR=CR+PR+SD) |
|
| E.2.2 | Secondary objectives of the trial |
To estimate Overall Objective Response Rate (ORR=CR+PR).
• To estimate Progression-Free Survival (PFS) and Overall Survival (OS).
SOP-210-G T65 GEL Clinical Study Protocol 3 (79)
Version 1, Date: 15 November 2005
Clinical Study Protocol
Study Code D4200C00075
Date 6th June 2007
The safety objective is:
• To further characterise the safety profile of vandetanib at 300 mg daily dose.
The quality of life objective is:
• To describe quality of life (QL) over time in mesothelioma patients receiving either vandetanib or vinorelbine. The primary endpoint is to compare between the two arms the proportion of patients with a clinically meaningful change in symptom burden from baseline to week 12. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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. |
|
| E.4 | Principal 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 cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
19. Receipt of any investigational agents within 30 days prior to commencing study treatment
20. Last radiation therapy within the last 4 weeks before the start of study therapy, except palliative radiotherapy at focal sites. These irradiated sites may not be used as target lesions.
21. Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy
22. Previous enrolment or randomization of treatment in the present study
23. Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
24. Involvement in the planning and conduct of the study (applies to both AstraZeneca staff or staff at the study site) |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Incidence of controlled disease (CR/PR/SD) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | Yes |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| Trial closure is defined as 6 months after the initiation of trial treatment in the last patient. This date will be used for the evaluation or censure of data for the trial endpoints. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 11 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 11 |
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