E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Following initial surgery (either debulking cytoreductive surgery or a biopsy if the patient has FIGO stage IV disease and there is no planned surgery before disease progression) patients with newly diagnosed FIGO stage I or IIa (Grade 3 or clear cell histology only), or FIGO stage IIb - IV (all grades and all histological types) epithelial ovarian, fallopian tube or primary peritoneal cancer, in whom no further surgery prior to disease progression is planned |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
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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 assess whether, in epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinoma, the addition of a specific new targeted anti-cancer treatment, bevacizumab, to the current international standard chemotherapy of carboplatin and paclitaxel, will improve progression free. Bevacizumab is a new type of treatment which works by interfering with the development of tumour blood vessels. It has already been licensed for use in combination with chemotherapy in colorectal cancer, and looks to have a promising role in other solid tumours. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives of the trial include the effect of the addition of bevacizumab on overall survival of the patients, their response rates and duration of response. The trial will also assess the impact of the addition of bevacizumab on the safety and toxicity of the therapy, as well as any effects on the quality of life of the patients, both while recieving the treatment and afterwards. Also, as with any new and expensive drug therapy, the cost of any improvements in outcome are important to quantify and this study will incorporate an analysis of pharmacoeconomics. There will also be associated laboratory based 'translational research' studies aiming to further investigate molecular factors that may be predictors of response and/or prognosis.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age over 18 (as standard treatments not licensed for use in those under 18 years)
- Written informed consent and able to comply with the protocol
- Histologically confirmed high risk FIGO stage I and II a (grade 3 or clear cell histology), or FIGO stage IIb – IV (all grades, all histological types) epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer
- Patients should have already undergone cytoreductive surgery and not be planned for any further surgical debulking prior to disease progression. Patients with stage IV disease in whom surgical debulking was not appropriate are eligible providing other criteria are fulfilled
- Patients able to receive protocol treatment
- ECOG performace status 0-2
- Life expectancy > 12 weeks
- Patients fit enough to begin treatment within 6 weeks of surgery - Urine dipstick for proteinuria < 2+ (If urine dipstick is > or = 2+, 24 hour urine must demonstrate < or = 1 g of protein)
-Adequate bone marrow, renal and liver function |
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E.4 | Principal exclusion criteria |
- Non epithelial ovarian cancer or borderline tumours
- Planned intraperitoneal therapy
- Surgery (including open biopsy), or radiotherapy within the last 4 weeks prior to first dose of bevacizumab or anticipation of interval cytoreductive surgery during study treatment
- Malignancies other than ovarian cancer within 5 years prior to randomisation, except for adequately treated carcinoma in situ of the cervix and/or basal cell skin cancer and/or early endometrial carcinoma
- Uncontrolled hypertension
- Previous CVA, TIA or sub arachnoid haemorrhage within 6 months prior to randomisation
- MI or unstable angina within 6 months prior to randomisation
- History of thrombotic or haemmorhagic disorder
- Previous gastrointestinal perforation and/or clinical suspicion of frank or impending bowel obstruction
- Current or recent (within 10 days of first dose of study treatment) use of aspirin > 325 mg/day
- Current or recent (within 10 days prior to study treatment start) use of full-dose oral or parenteral anticoagulants or thrombolytic agent for therapeutic purposes (except for line patency) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free Survival |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life; Translational Research |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Against standard chemotherapy and a period of observation |
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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 | 50 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 270 |
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 | 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 trial will be considered closed when data on overall survival are sufficiently mature for primary publication. This is expected to occur 3 years after the recruitment of the last patient (assuming that, as expected, the duration of the recruitment period is 2 years). |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |