A Phase 2, Multi-Center, Double-Blind, Placebo Controlled, Randomized Study of Ombrabulin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer Treated With Carboplatin/Paclitaxel
1. Signed informed consent.
2. At least 18 years of age.
3. Histological and/or cytological diagnosis of epithelial ovarian carcinoma, fallopian
tube cancer, or primary peritoneal carcinoma.
4. Completion of maximum one previous line of chemotherapy containing a platinum agent.
Neoadjuvant/adjuvant treatment that include a surgical procedure will be considered
as one line if platinum-based.
5. Documented sensitivity to a platinum based chemotherapy regimen.
"Platinum-sensitivity" is defined by a relapse more than 6 months after last dose of
6. Measurable progressive disease: Measurable disease (as defined by RECIST 1.1) is
defined as at least one lesion that can be accurately measured in at least one
dimension (longest diameter to be recorded). Each lesion must be at least 10mm when
measured by computed tomography (CT) or magnetic resonance imaging (MRI). Lymph nodes
must be >15 mm in short axis when measured by CT or MRI. In case of a single
measurable lesion, this should not be previously irradiated.
7. ECOG performance status ≤2
8. Life expectancy more than 12 weeks
1. History of uncontrolled brain metastases, spinal cord compression, or carcinomatous
2. History of another neoplasm. Adequately treated basal cell or squamous skin cancer,
or in situ cervical cancer, or any other cancer from which the patient has been
disease-free for >5 years are allowed.
3. Participation in another clinical trial and any concurrent treatment with any
investigational drug or anti-tumor therapy or radiotherapy within 21 days prior to
randomization (or 28 days for those therapies with a schedule of administration every
4 weeks and except for nitrosoureas, mitomycin which may not be used up to 6 weeks
prior to the first cycle provided that patients do not have residual signs of any
toxicity). No wash-out is required for hormonotherapy which has to be discontinued
before the first cycle.
4. Any severe acute or chronic medical condition, which could impair the ability of the
patient to participate in the study or interfere with interpretation of study
5. Pregnancy or breast-feeding. Positive serum or urine pregnancy test prior to
6. Patient with reproductive potential who do not agree to use accepted and effective
method of contraception during the study treatment period and for at least 6 months
after the completion of the study treatment. The definition of "effective method of
contraception" will be based on the investigator's judgment. Effective method of
contraception should also be adapted to local regulations.
7. Inadequate organ function including: neutrophils <1.5 x 10^9/L; platelets <100 x
10^9/L; creatinine ≥ 1.5 ULN. If creatinine ≥ ULN, the calculated creatinine
clearance should be ≥ 60 ml/min (as per Cockcroft Formula). Total bilirubin not
within normal limit and ALT/AST/AP >2.5 times the upper normal limits of the
institutional norms. An increase of AP up to grade 2 would be accepted only if this
increase is related to the presence of bone metastases. Bone specific isoenzyme AP
should be evaluated.
8. Urine protein-creatinin ratio (UPCR) >1 (urinanalysis on morning spot urine) or
proteinuria >500 mg/24h
9. Pre-existing peripheral neuropathy > grade 1 according to the NCI CTCAE V.4.03
10. Pre-existing hearing impairment > grade 1
11. Known hypersensitivity due to taxanes and /or polysorbate 80 or any other
compound/excipients of the study drug combination
12. Discontinuation of previous treatment with paclitaxel and/or carboplatin for toxicity
13. Other serious illness or medical conditions such as (but not restricted):
- Active infection
- Superior vena cava syndrome
- Pericardial effusion requiring intervention (drainage)
14. Documented medical history of myocardial infarction, documented angina pectoris,
arrhythmia especially severe conduction disorder such as second or third-degree
atrioventricular block, stroke, or history of arterial or venous thrombo-embolism
within the past 6 months still requiring anticoagulants.
15. Cardiac Troponin at levels that exceed the normal ranges values defined by the
16. Uncontrolled hypertension within 3 months prior to study treatment or patient with
organ damage related to hypertension.
17. Patient with LVEF value lower than institution inferior normal limit, evaluated by
echocardiography or angiocardiography
18. 12-lead ECG:
- Infarction Q-wave,
- ST segment depression or elevation ≥1 mm in at least 2 contiguous leads
- QT/QTc-Time > 450ms
The above information is not intended to contain all considerations relevant to a
patient's potential participation in a clinical trial.