E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Epithelial ovarian cancer, fallopian tube or primary peritoneal carcinoma |
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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 | 10033128 |
E.1.2 | Term | Ovarian cancer |
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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 | 10016180 |
E.1.2 | Term | Fallopian tube cancer |
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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 | 10061344 |
E.1.2 | Term | Peritoneal neoplasm |
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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 evaluate progression-free survival (PFS) in patients treated with carboplatin and weekly paclitaxel plus bevacizumab as first-line treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate: • Overall response rate (ORR): o By RECIST and 50% CA-125 response criteria (“responders”) o By RECIST only (“RECIST responders”) o By 50% CA-125 response criteria only (“CA-125 responders”)
• Duration of response (DR; by RECIST and 50% CA-125 response criteria)
• Overall survival (OS)
• Biological progression-free interval (BPFI)
• Safety and tolerability.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent obtained prior to initiation of any study-specific procedures and treatment as confirmation of the patient’s awareness and willingness to comply with the study requirements.
2. Female patients ≥18 years of age.
3. Patients with histologically confirmed and documented, high risk International Federation of Gynecologic Oncology (FIGO) Stage I–IIa (only if grade 3 / poorly differentiated) or Stage IIb–IV (any grade) epithelial ovarian carcinoma, fallopian tube carcinoma or primary peritoneal carcinoma. or Clear cell carcinoma regardless of the FIGO stage (clear cell carcinoma is defined as either ≥50% clear cell elements present or reported as clear cell carcinoma by the local pathologist). or Previous early stage epithelial ovarian or fallopian tube carcinoma treated with surgery alone. If the patient has abdomino-pelvic recurrence, they are eligible to participate in the trial as long as no further surgery is planned prior to disease progression.
4. Patients should have already undergone surgical debulking, by a surgeon experienced in the management of ovarian cancer, with the aim of maximal surgical cytoreduction according to the GCIG Conference Consensus Statement.1 There must be no planned surgical debulking prior to disease progression. Patients with stage III and IV disease in whom initial surgical debulking was not appropriate will still be eligible providing • the patient has a histological diagnosis and • debulking surgery prior to disease progression is not foreseen
5. ECOG Performance Status of 0–2.
6. Life expectancy of ≥ 12 weeks.
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E.4 | Principal exclusion criteria |
1. Non-epithelial Ovarian Cancer, including malignant mixed Müllerian tumours. 2. Ovarian tumours with low malignant potential 3. Previous systemic anti-cancer therapy for ovarian cancer. 4. History or evidence of synchronous primary endometrial carcinoma, unless all of the following criteria related to the endometrial carcinoma are met: • stage ≤Ib • no more than superficial myometrial invasion • no lymphovascular invasion • not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma). 5. Other malignancy within the last 5 years, except for adequately treated carcinoma in situ of the cervix or squamous carcinoma of the skin, or adequately controlled limited basal cell skin cancer. 6. Any prior radiotherapy to the pelvis or abdomen. 7. Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose or planned during 13 months from the start of study treatment (including 12 months of bevacizumab therapy plus 4 weeks post-bevacizumab therapy). 8. Previous exposure to mouse CA-125 antibody. 9. Current or recent (within 10 days prior to the first study drug dose) chronic daily treatment with aspirin (>325 mg/day). 10. Current or recent (within 10 days prior to the first study drug dose) use of full-dose oral or parenteral anticoagulant or thrombolytic agent for therapeutic purposes (except for line patency, in which case international normalized ratio [INR] must be maintained below 1.5). 11. Current or recent (within 30 days of first study dosing) treatment with another investigational drug or participation in another investigational study. 12. Planned intraperitoneal cytotoxic chemotherapy. 13. Inadequate bone marrow function: ANC: <1.5 x 10^9/l, or platelet count <100 x 10^9/l or Haemoglobin <9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9 g/dl. 14. Inadequate coagulation parameters: • activated partial thromboplastin time (APTT) >1.5 xULN or • INR >1.5 15. Inadequate liver function, defined as: • serum (total) bilirubin >1.5 x the upper limit of normal (ULN) for the institution • AST/SGOT or ALT/SGPT >2.5 x ULN. 16. Inadequate renal function, defined as: • serum creatinine >2.0 mg/dl or >177 micromol/l • urine dipstick for proteinuria >2+. Patients with ≥2+ proteinuria on baseline dipstick analysis should undergo a 24-hour urine collection and must demonstrate ≤1g of protein in their 24-hour urine collection. Prior or concomitant conditions or procedures: 17. History or evidence of brain metastases or spinal cord compression. A CT or MRI of the brain and/or MRI of the spinal cord must be performed within 4 weeks prior to first study treatment if the presence of metastases or compression is suspected, respectively. 18. Pre-existing peripheral neuropathy ≥CTC grade 2. 19. Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start. 20. Women of childbearing potential (defined as <2 years after last menstruation and not surgically sterile) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly) during the study and for 6 months after the last bevacizumab administration. 21. History or evidence of thrombotic or hemorrhagic disorders; including cerebrovascular accident (CVA) / stroke or transient ischemic attack (TIA) or sub-arachnoid haemorrhage within ≤6 months prior to the first study treatment). 22. Uncontrolled hypertension (sustained systolic >150 mm Hg and/or diastolic >100 mm Hg despite antihypertensive therapy) or clinically significant (i.e. active) cardiovascular disease, including: • myocardial infarction or unstable angina within ≤6 months prior to the first study treatment • New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF) • serious cardiac arrhythmia requiring medication • peripheral vascular disease ≥grade 3 23. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to the first study treatment. 24. Non-healing wound, ulcer or bone fracture. Patients with granulating incisions healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require three weekly wound examinations. 25. Significant traumatic injury during the 4 weeks preceding the first dose of bevacizumab. 26. Known hypersensitivity to any of the study drugs or excipients. 27. Evidence of any other medical conditions, physical examination or laboratory findings that may interfere with the planned treatment, affect patient compliance or place the patient at high risk from treatment-related complications.
please refer to the protocol for more details |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary study endpoint is PFS, defined as the time from first study drug dosing to the first documented disease progression or death, whichever occurs first. The median PFS together with the one-sided 95% confidence interval will be estimated by the nonparametric method of R.Brookmeyer and J.Crowley. |
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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 | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability and biomarkers analysis |
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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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |