E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
advanced ovarian cancer sensitive to platinum based chemotherapy
cáncer de ovario avanzado sensible a la quimioterapia basada en platino |
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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 | HLT |
E.1.2 | Classification code | 10033129 |
E.1.2 | Term | Ovarian neoplasms malignant (excl germ cell) |
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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 compare the objective tumour response rate, as evaluated according to RECIST guidelines, in patients treated with AZD0530 in combination with carboplatin plus paclitaxel versus carboplatin plus paclitaxel alone |
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E.2.2 | Secondary objectives of the trial |
1. To investigate the safety and tolerability of AZD0530 in combination with carboplatin plus paclitaxel versus carboplatin plus paclitaxel alone. 2. To compare progression-free survival in patients treated with AZD0530 in combination with carboplatin plus paclitaxel versus carboplatin plus paclitaxel alone. 3. To investigate the steady-state pharmacokinetics (PK) of AZD0530 and the N desmethyl metabolite (M594347) in combination with carboplatin plus paclitaxel. 4. To measure plasma concentrations of total platinum 24 hours after administration of carboplatin to enable the estimation of carboplatin AUC.
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: A Phase II, Double-blind, Placebo-controlled, Multi-centre, Randomised Study of AZD0530 in Patients with Advanced Ovarian Cancer Sensitive to Platinum-based Chemotherapy (OVERT-1)
Date: 27 September 2007
Objetive: To obtain a blood sample for DNA extraction for future pharmacogenetic analysis and other potential correlative markers of AZD0530 activity. |
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E.3 | Principal inclusion criteria |
1. Provision of signed, written informed consent 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 5. Radiological evidence of disease recurrence or progression at least 6 months following treatment cessation of first or second line platinum containing therapy (including platinum based maintenance therapy) 6. Documented non-measurable or measurable lesion according to RECIST criteria assessed by Computerised Tomography (CT) or Magnetic Resonance Imaging (MRI) 7. World Health Organisation (WHO) performance status 0 to 2 8. Estimated life expectancy of more than 12 weeks 9. Evidence of non-childbearing status: negative pregnancy test within 7 days of study treatment if of childbearing potential, or postmenopausal status (defined by any one of the following: natural menopause with last menses >1 year ago; radiation-induced oophorectomy with last menses >1 year ago, chemotherapy-induced menopause with >1 year interval since last menses) or surgical sterilisation (bilateral oophorectomy or hysterectomy) 10. For inclusion in the optional pharmacogenetic research, patients must fulfil the following criterion: Provision of informed consent for pharmacogenetic research If a patient declines to participate in the pharmacogenetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in the Clinical Study Protocol, so long as they consent.
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E.4 | Principal exclusion criteria |
1. Clinical evidence of central nervous system (CNS) metastases 2. Non-epithelial ovarian cancer, including malignant mixed Mullerian tumours and mucinous carcinoma of the peritoneaum 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) 5. Inadequate bone marrow reserve as demonstrated either by an absolute neutrophil count <1.5 x 10 to the power of 9/L or platelet count <100 x 10 to the power of 9/L 6. Haemoglobin ≤9 g/dL (5.59 mMol/L) 7. Inadequate liver function as demonstrated by serum bilirubin ≥2 times the upper limits of reference range (ULRR), alanine aminotransferase (ALT), aspartate aminotransferase (AST) or ALP ≥2.5 times the ULRR (ALP ≥5 times the ULRR if judged by the investigator to be related to liver metastases) 8. Patients with estimated GFR</=50ml/min calculated by the Cockroft and Gault formula (Appendix M) 9. Last dose of anti-cancer therapy received within 14 days prior to the first dose of treatment with study drug. If insufficient wash-out time has not occurred due to schedule or PK properties, a longer wash-out period will be required according to expected time to anti-tumour effect, or known duration and time to reversibility of drug related AEs, as agreed upon by AstraZeneca and the Investigator 10. Received more than two previous chemotherapy regimens for treatment of ovarian cancer 11. Evidence of uncontrolled systemic conditions (eg, severe hepatic impairment) or current unstable or uncompensated respiratory or cardiac conditions which makes it undesirable for the patient to participate in the study or which could jeopardise compliance with the protocol 12. Any other concurrent condition which in the investigator’s opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol 13. Pregnant or breast-feeding women 14. Unwillingness to use an acceptable method of contraception while on study (for women of child bearing potential) and for three months after cessation of dosing with AZD0530. Post-menopausal status will be considered adequate evidence of non-childbearing potential and is defined as any 1 of the following: natural menopause with last menses >1 year ago, radiation induced oophorectomy with last menses >1 year ago, chemotherapy-induced menopause with >1 year interval since last menses or surgical sterilisation (bilateral oophorectomy or hysterectomy) 15. Unresolved toxicity ≥CTCAE grade 2 from previous anti-cancer therapy except alopecia 16. Symptomatic peripheral neuropathy ≥NCIC-CTC grade II 17. Patients believed to have a known immunodeficiency syndrome 18. Resting ECG with measurable QTc interval of >480 msec at 2 or more time points within a 24 hour period 19. Current use or previous use within specified time period (detailed in CSP Appendix E) of drugs or herbal supplements known to be potent inducers or inhibitors of CYP3A4 20. Known hypersensitivity to AZD0530, its excipients, or drugs in its class 21. Cannot be adequately followed up for the duration of their study participation. 22. Participation in another study with an investigational product within the previous 90 days or participation in a previous clinical study within 30 days prior to study entry 23. Risk (in the investigator’s opinion) of transmitting, through blood or other body fluids, the agents responsible for Acquired Immunodeficiency Syndrome, hepatitis B, or hepatitis C. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome variable for this study is objective tumour response rate (as per RECIST) |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
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 | 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 | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
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 |
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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
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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 | 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 |