Clinical trial NCT01332656: Study of Ombrabulin in Patients With Platinum-Sensitive Recurrent Ovarian Cancer Treated With Carboplatin/Paclitaxel
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ovarian Cancer Recurrent
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-04-11
Enrollment: 154
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Primary Objective:

- 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.

Secondary Objectives:

* To compare the overall survival (OS) between the 2 treatment arms
* To compare the objective response rate (RR) between the 2 treatment arms

Detailed description: Treatment will continue until disease progression or unacceptable toxicity or consent withdrawal. A minimum of 6 cycles of the combined therapies should be administered, unless progression occurs before or safety reasons cause the discontinuation of one or two drugs of the combination therapies. In case of no progression, it will be investigator's decision to continue or not the study treatment after 6 cycles according to his clinical practice.

Eligibility criteria: 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 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

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 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 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 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 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 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.

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: approximately 24 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: approximately 24 months
measure: Objective Response Rate (RR)
timeFrame: approximately 24 months
Other outcomes:
Locations:
city: Burbank
country: United States
facility: Investigational Site Number 840007
state: California
city: New Haven
country: United States
facility: Investigational Site Number 840001
state: Connecticut
city: Fort Meyers
country: United States
facility: Investigational Site Number 840202
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number 840009
state: Georgia
city: Boston
country: United States
facility: Investigational Site Number 840002
state: Massachusetts
city: Haine-Saint-Paul
country: Belgium
facility: Investigational Site Number 056002
city: Kortrijk
country: Belgium
facility: Investigational Site Number 056005
city: Leuven
country: Belgium
facility: Investigational Site Number 056001
city: Namur
country: Belgium
facility: Investigational Site Number 056003
city: Novy Jicin
country: Czech Republic
facility: Investigational Site Number 203003
city: Olomouc
country: Czech Republic
facility: Investigational Site Number 203002
city: Praha 2
country: Czech Republic
facility: Investigational Site Number 203001
city: Zlin
country: Czech Republic
facility: Investigational Site Number 203004
city: Bordeaux
country: France
facility: Investigational Site Number 250006
city: Caen Cedex 05
country: France
facility: Investigational Site Number 250004
city: Lyon
country: France
facility: Investigational Site Number 250001
city: Paris Cedex 4
country: France
facility: Investigational Site Number 250002
city: Villejuif
country: France
facility: Investigational Site Number 250003
city: München
country: Germany
facility: Investigational Site Number 276001
city: Genova
country: Italy
facility: Investigational Site Number 380004
city: Milano
country: Italy
facility: Investigational Site Number 380003
city: Roma
country: Italy
facility: Investigational Site Number 380001
city: Krakow
country: Poland
facility: Investigational Site Number 616002
city: Poznan
country: Poland
facility: Investigational Site Number 616004
city: Rybnik
country: Poland
facility: Investigational Site Number 616003
city: Warszawa
country: Poland
facility: Investigational Site Number 616005
city: Warszawa
country: Poland
facility: Investigational Site Number 616001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643001
city: Saint-Petersburg
country: Russian Federation
facility: Investigational Site Number 643004
city: Barcelona
country: Spain
facility: Investigational Site Number 724002
city: Madrid
country: Spain
facility: Investigational Site Number 724003
city: Madrid
country: Spain
facility: Investigational Site Number 724001
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site Number 804003
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804005
city: Kharkov
country: Ukraine
facility: Investigational Site Number 804004
city: Lviv
country: Ukraine
facility: Investigational Site Number 804002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: