A MULTICENTER STUDY IN PATIENTS WITH STAGE III-IV EPITHELIAL OVARIAN CANCER TREATED WITH CARBOPLATIN/PACLITAXEL WITH BEVACIZUMAB: CLINICAL AND BIOLOGICAL PROGNOSTIC FACTORS
- Female patients ≥18 years of age.
- Patients with histologically confirmed epithelial ovarian carcinoma, fallopian tube
carcinoma or primary peritoneal carcinoma, including mixed Mullerian Tumours Or
Recurrent early stage epithelial ovarian or fallopian tube carcinoma treated with
- FIGO stage IIIB & C or IV
- ECOG Performance Status of 0-2.
- Life expectancy of at least 12 weeks.
- 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.
- Availability of tumour samples for molecular analyses
- Ovarian tumours with low malignant potential (i.e. borderline tumours)
- Previous systemic anti-cancer therapy for advanced ovarian cancer.
- History or evidence of brain metastases or spinal cord compression.
- History or evidence of synchronous primary endometrial carcinoma, unless all of the
following criteria related to the endometrial carcinoma are met:
- stage ≤Ia
- no more than superficial myometrial invasion
- no lymphovascular invasion
- not poorly differentiated (grade 3 or papillary serous or clear cell carcinoma).
- 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.
- Any prior radiotherapy to the pelvis or abdomen.
- Surgery (including open biopsy) within 4 weeks prior to the first bevacizumab dose or
planned (In this case the patient can be enrolled but the administration of
bevacizumab should be omitted at first cycle).
- 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 central venous access patency, in which case international
normalized ratio [INR] must be maintained below 1.5). Post operative prophylaxis with
low molecular weight heparin sc is allowed.
- Current or recent (within 30 days of first study dosing) treatment with another
- Inadequate bone marrow function: ANC: <1.5 x 109/l, or platelet count <100 x 109/l or
Haemoglobin <9 g/dl. Patients may be transfused to maintain haemoglobin values ≥9
- Inadequate coagulation parameters:
- activated partial thromboplastin time (APTT) >1.5 xULN or
- INR >1.5
- Inadequate liver function, defined as:
- serum (total) bilirubin >1.5 x the upper limit of normal (ULN) for the
- AST/SGOT or ALT/SGPT >2.5 x ULN.
- Inadequate renal function, defined as serum creatinine >2.0 mg/dl or >177 micromol/l
- Proteinuria >1g in a 24-hour urine collection (to be performed only among patients
who showed a ≥3+ at urine dipstick).
- Pregnant or lactating patients.
- 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).
- 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
- New York Heart Association (NYHA) grade II or greater congestive heart failure
- serious cardiac arrhythmia requiring medication (with the exception of atrial
fibrillation or paroxysmal supraventricular tachycardia)
- peripheral vascular disease ≥grade 3 (i.e. symptomatic and interfering with
activities of daily living requiring repair or revision).
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 6 months prior to the first study treatment.
- Non-healing wound, ulcer or bone fracture. Patients with granulating incisions
healing by secondary intention with no evidence of fascial dehiscence or infection
are eligible but require three weekly wound examinations.
- Evidence of any other medical conditions (such as psychiatric illness, peptic ulcer,
etc.), physical examination or laboratory findings that may interfere with the
planned treatment, affect patient compliance or place the patient at high risk from