E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Following primary cytoreductive surgery, patients with newly diagnosed FIGO stage IIB - IV (all grades and all histological types) epithelial ovarian cancer, fallopian tube carcinoma or primary peritoneal carcinomas with indication for a platin/paclitaxel chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
After operation of primary tumor, patients with newly diagnosed FIGO stage IIB - IV (all grades and all histological types) ovarian cancer with indication for a platin/paclitaxel chemotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10033128 |
E.1.2 | Term | Ovarian cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 progression-free survival (PFS) (by RECIST v1.1, clinical or symptomatic) of patients randomized to front-line paclitaxel/carboplatin with bevacizumab for 15 months or 30 months. |
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E.2.2 | Secondary objectives of the trial |
- Objective response rate by RECIST v1.1
- Overall survival
- Health related Quality of life using EORTC QLQ-C30 and QLQ-OV28 questionnaires
- Safety and tolerability
Further exploratory outcome measures on ancillary studies will include:
- Translational Sub Studies
- Complementary and Alternative Treatment Qestionnaires |
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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 |
Improved utilisation of resources and optimisation of quality of care through internet-based second opinion pathology - standardized in an optimized ovarian cancer network (AGO VISION-1).
The aim of the VISION protocol is to establish a new infrastructure that may provide a high throughput second opinion pathology for ovarian carcinoma with a time necessary of only 10 days.
Pharmacogenomic sub-study
Blood samples: The aim is to identify the prognostic value of genetic markers in view of progression free survival and toxicity after treatment with bevacizumab and paclitaxel/carboplatin.
Tumor tissue block: Analyzing of the tumor tissue and the genetic
information of the tumor (DNA/RNA) in view of existence of specific structures and molecules which could be of importance for diagnosis, assessment of prognosis and new treatment possibilities.
Complementary and Alternative Treatment Questionnaires
This sub-study will be identify the relationship between progress of the disease and physical activity, quality of life and physical activity as well as quality of life and the use of complementary and alternative treatment. |
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E.3 | Principal inclusion criteria |
- Written informed consent and patients awareness
and willingness to comply with the study
requirements
- Primary diagnosis is confirmed by specialized
pathology review (Germany only)
- Age ≥ 18 years
- Histologically confirmed, newly diagnosed epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma and FIGO stage IIB - IV (all grades and all histological types)
- Patients should have already undergone surgical debulking and no planned surgical debulking prior to disease progression. Patients
with stage III and IV disease in whom initial surgical debulking was not
appropriate or possible are eligible providing other criteria are fulfilled
- Patients able to commence cytotoxic
chemotherapy within 8 weeks of cytoreductive surgery
- ECOG performance status 0-2
- Life expectancy > 3 months
- Adequate bone marrow function, coagulation parameters, liver function, postoperative glomerulare filtration rate (based on the Cockroft-Gault or Jelliffe formula)
- Urine dipstick for proteinuria < 2+. If
urine dipstick is ≥ 2+, 24 hour urine must
demonstrate ≤ 1 g of protein in 24 hours |
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E.4 | Principal exclusion criteria |
- Non-epithelial origin of the ovary, the fallopian
tube or the peritoneum
- Borderline tumours and FIGO stage IA – IIA
- Planned intraperitoneal cytotoxic chemotherapy
- Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab or anticipation of interval cytoreductive surgery during study treatment
- Uncontrolled hypertension
- Any previous radiotherapy to the abdomen or pelvis
- Previous Cerebro-Vascular Accident, Transient Ischaemic Attack or Sub-Arachnoid Haemorrhage within 6 months prior to randomisation
- 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 non-melanomatous skin cancer, carcinoma in situ of the breast and/or early endometrial carcinoma
- Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless other criteria are fulfilled
- Non healing wound, active ulcer or bone fracture
- History or evidence of thrombotic or hemorrhagic disorders
- Clinically significant cardiovascular disease, including Myocardial infarction or unstable angina within 6 months of randomisation, NYHA ≥ Grade 2, poorly controlled cardiac arrhythmia despite medication, Grade ≥ 3 peripheral vascular disease
- Current or recent (within 10 days prior to randomisation) chronic use of aspirin > 325 mg/day
- Current or recent (within 10 days prior to randomisation) 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 (PFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At least 523 PFS events have been observed (appr. 4.5 years). |
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E.5.2 | Secondary end point(s) |
- Objective response rate (ORR)
- Overall survival (OS)
- Quality of life (QoL)
- Safety and tolerability
Further exploratory outcome measures on ancillary studies will include:
- Translational Sub Studies
- Complementary and Alternative Treatment Questionnaires |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
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 | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of life, Translational Research, Complementary and Alternative Treatment Questionnaires |
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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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 100 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 150 |
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 | No |
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 |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Norway |
Sweden |
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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
|
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 | 5 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 5 |