A multi-centre, open-label, randomised, twoarm Phase III trial to evaluate optimal treatment duration of first-line bevacizumab in combination with carboplatin and paclitaxel in patients with primary epithelial ovarian, fallopian tube or peritoneal cancer.
- Conditions
- Following primary cytoreductive surgery, patients with newly diagnosed FIGO stage IIb -IV (all grades and all histological types) epithelial ovarian cancer (EOC), fallopian tubecarcinoma (FTC) or primary peritoneal carcinomas (PPC) with indication for a platin/paclitaxel chemotherapy.MedDRA version: 21.0Level: LLTClassification code 10016412Term: Female reproductive neoplasm NOSSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-001015-32-SE
- Lead Sponsor
- AGO Research GmbH, AGO Study Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Female
- Target Recruitment
- 900
1. Signed written informed consent obtained prior to initiation of any studyspecific
procedures and treatment as confirmation of the patients awareness and willingness to comply with the study requirements.
2. Primary diagnosis is confirmed by specialized pathology review (Germany only)
3. Females aged = 18 years
4. Histologically confirmed, newly diagnosed
• Epithelial ovarian carcinoma
• Fallopian tube carcinoma
• Primary peritoneal carcinoma
AND FIGO stage IIb - IV (all grades and all histological types)
5. 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. 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 or possible will still be eligible providing
• the patient has a histological diagnosis and
• debulking surgery prior to disease progression is not foreseen
6. Patients must be able to commence cytotoxic chemotherapy within 8 weeks of cytoreductive surgery. The first dose of bevacizumab can be omitted in both arms if the investigator decides to start chemotherapy within 4 weeks of surgery
7. ECOG performance status (PS) 0-2
8. Life expectancy > 3 months
9. Adequate bone marrow functiona (within 14 days prior to randomization)
• Absolute Neutrophil Count (ANC) = 1.5 x 109/L
• Platelets (PLT) = 100 x 109/L
• Hemoglobin (Hb) = 9 g/dL (can be post-transfusion)
10. Adequate coagulation parametersa (within 14 days prior to randomization)
• Patients not receiving anticoagulant medication who have an International Normalised Ratio (INR) = 1.5 and an Activated ProThrombin Time (aPTT) = 1.5 x ULN
• The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to institution medical standard) and the patient has been on a stable dose of anticoagulants for at least two weeks at the time of randomization
11. Adequate liver functiona (within 14 days prior to randomization)
• Serum bilirubin = 1.5 x ULN
• Serum transaminases = 2.5 x ULN
12. Urine dipstick for proteinuria < 2+. If urine dipstick is = 2+, 24 hour urine must
demonstrate = 1 g of protein in 24 hours
13. Adequate postoperative glomerulare filtration rate > 40 ml/min (estimates based on the Cockroft-Gault or Jelliffe formula are sufficient)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 900
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Non-epithelial origin of the ovary, the fallopian tube or the peritoneum
2. Borderline tumours (tumours of low malignant potential) and FIGO stage Ia – IIa
tumours
3. Planned intraperitoneal cytotoxic chemotherapy
4. Prior systemic anti-cancer therapy for ovarian cancer (for example chemotherapy,
monoclonal antibody therapy, tyrosine kinase inhibitor therapy or hormonal therapy)
5. Surgery (including open biopsy) within 4 weeks prior to anticipated first dose of bevacizumab (allowing for the fact that bevacizumab can be omitted from the first cycle of chemotherapy).
It is strongly recommended that an interval of 7 days is left between the insertion of any central venous access devices (CVADs) and the onset of bevacizumab treatment.
6. Any planned surgery during the study treatment period plus 4 additional weeks to allow for bevacizumab clearance
7. Uncontrolled hypertensionb (sustained elevation of BP systolic > 150mmHg and/or diastolic > 100mmHg despite antihypertensive therapy)
8. Any previous radiotherapy to the abdomen or pelvis
9. Significant traumatic injury during 4 weeks preceding the potential first dose of bevacizumab
10. History or clinical suspicion of brain metastases or spinal cord compression. CT/MRI of the brain is mandatory (within 4 weeks prior to randomization) in case of suspected brain metastases. Spinal MRI is mandatory (within 4 weeks prior to randomization) in case of suspected spinal cord compression
11. History or evidence upon neurological examination of central nervous system (CNS) disease, unless adequately treated with standard medical therapy e.g. uncontrolled seizures
12. Previous Cerebro-Vascular Accident (CVA), Transient Ischaemic Attack (TIA) or Sub-Arachnoid Haemorrhage (SAH) within 6 months prior to randomization
13. Fertile woman of childbearing potential not willing to use adequate contraception
(oral contraceptives, intrauterine device or barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) for the study duration and at least 6 months afterwards
14. Pregnant or lactating women
15. Treatment with other investigational agents, or participation in another clinical
trial testing a drug within the past 4 weeks before start of therapy concomitantly with this trial
16. Malignancies other than ovarian cancer within 5 years prior to randomization, 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
as specified below. Patients may have received previous adjuvant chemotherapy for other malignancies e.g. breast or colorectal carcinoma if diagnosed over 5 years ago with no evidence of subsequent recurrence
17. Patients with synchronous primary endometrial carcinoma, or a past history of primary endometrial carcinoma, are excluded unless ALL of the following criteria for describing the endometrial carcinoma are met
• Disease stage FIGO stage = IA (tumour invades less than one half of the myometrium)
18. Known hypersensitivity to bevacizumab and its excipients, Chinese hamster ovary
cell products or other recombinant human or humanised antibodies
19. Non healing wound, active ulcer or bone fracture. Patients with granulating incisions
healing by secondary intention with no evidence of facial dehiscence or infection are eligible but require 3 weekly wound examinations
20. History or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method