E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10066697 |
E.1.2 | Term | Ovarian cancer recurrent |
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 demonstrate an improvement in Progression-Free Survival (PFS) for ombrabulin versus placebo in patients with platinum-sensitive recurrent ovarian cancer (OC) treated with paclitaxel and carboplatin. |
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E.2.2 | Secondary objectives of the trial |
- To compare the overall survival (OS) between the 2 treatment arms
- To compare the objective response rate (RR) between the 2 treatment arms |
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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 |
Tumoral pharmacogenomic sub-study (please refer to the protocol, version 1 (el. 4.0), dated 26 January 2011)
The main objective of this sub-study is to analyse a set of biological biomarkers in order to identify a potential
predictive signature of efficacy for ombrabulin in combination with taxanes and platinum salts. |
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E.3 | Principal inclusion criteria |
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 platinum based chemotherapy.
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 10 mm³ 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 |
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E.4 | Principal exclusion criteria |
1. History of uncontrolled brain metastases, spinal cord compression, or carcinomatous meningitis.
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 exception 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 that 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 results.
5. Pregnancy or breast-feeding. Positive serum or urine pregnancy test prior to randomization.
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 Cockroft 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 reason
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 laboratory
16. Uncontrolled hypertension within 3 months prior to study randomization 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 >450 ms |
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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 |
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E.5.2 | Secondary end point(s) |
Overall Survival (OS)
Objective Response Rate (RR) |
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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 | Yes |
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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
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 |
Russian Federation |
Ukraine |
United States |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 28 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 28 |
E.8.9.2 | In all countries concerned by the trial days | 0 |