E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with advanced ovarian cancer who have relapsed following first-line platinum containing therapy (Patients may have received any other chemotherapy agent with the platinum agent). Relapse must have occurred at least 6 months after cessation of first-line treatment. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare progression-free survival in patients with advanced ovarian cancer treated with ZD4054 in combination with carboplatin and paclitaxel versus ZD4054 matched placebo in combination with carboplatin and paclitaxel. |
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E.2.2 | Secondary objectives of the trial |
1) To compare overall survival in patients with advanced ovarian cancer treated with ZD4054 in combination with carboplatin+paclitaxel versus placebo in combination with carboplatin+paclitaxel. 2. To compare the objective tumour response rate, as evaluated according to RECIST criteria in patients with advanced ovarian cancer treated with ZD4054 in combination with carboplatin+paclitaxel versus placebo in combination with carboplatin+paclitaxel. 3. To investigate the safety and tolerability of ZD4054 given in combination with carboplatin/paclitaxel in patients with advanced ovarian cancer. 4. To investigate the pharmacokinetics (PK) of ZD4054 in patients with advanced ovarian cancer as given in combination with carboplatin+paclitaxel. 5. To explore the effect of adding ZD4054 to a chemotherapy regimen of carboplatin+paclitaxel on patients’ health related quality of life (HRQoL). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Provision of informed consent prior to any study specific procedures 2. Females aged 18 years and older 3. Histologically proven diagnosis of: − Epithelial ovarian carcinoma − Fallopian tube carcinoma − Primary serous peritoneal carcinoma 4. Advanced disease not amenable to curative surgery or radiotherapy at the time of study entry with evidence of disease recurrence or progression at least 6 months following treatment cessation of first-line platinum-containing therapy and having stopped any maintenance therapy at least 30 days prior first dose of treatment with study drug (if applicable, excluding platinum-based maintenance therapy). 5. Radiologically documented measurable disease according to RECIST criteria assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) or radiologically documented non-measurable (but evaluable) disease. A non-measurable but evaluable patient is defined as a patient with a non-measurable soft tissue lesion (this includes bone lesions) that can be determined according to RECIST and documented via a CT or MRI scan. Patients with ascites and/or pleural/pericardial effusion only, are not considered as evaluable in this study 6. World Health Organisation (WHO) performance status 0 to 2 7. Estimated life expectancy of more than 16 weeks
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E.4 | Principal exclusion criteria |
Clinical evidence of central nervous system (CNS) metastases 2. Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneum 3. Tumour of borderline malignancy 4. A second primary malignancy (except in situ carcinoma of the cervix or adequately treated basal cell carcinoma of the skin) in the last 5 years 5. Inadequate bone marrow reserve as demonstrated either by an absolute neutrophil count <1.5 x 109/L or platelet count <100 x 109/L 6. Haemoglobin ≤9 g/dL (5.59 mMol/L) 7. Stage II, III or IV cardiac failure (classified according to New York Heart Association [NYHA] classification [see Appendix D]) or myocardial infarction within 6 months prior to study entry 8. Severe or frequent migrainous headaches |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective of this study is to compare progression-free survival in patients treated with ZD4054 on a background of carboplatin plus paclitaxel versus placebo on a background of carboplatin plus paclitaxel. |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
CA-125 progression;change in tumour size |
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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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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 | 14 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
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
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The end of the study will be defined as the final database lock. It is anticipated that the study will take 10 months to recruit all patients with a further 9 months of follow up until the primary analysis. It is then anticipated that a further 11 months of follow up will be required for the analysis of overall survival making a total study duration of 30 months; however exact timing of analyses and study completion is dependant on event rates. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |