The subjects who will participate to this clinical trial are cancer patients (i.e. patients with metastatic or locally advanced tumor of the lung, pancreas, stomach, colon/ rectum, bladder or ovary) at high risk for VTE and who are undergoing chemotherapy.
Conditions
Sponsors
sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Cancer patients: 1. With metastatic or locally advanced solid tumor of the lung, pancreas, stomach, colon/rectum, bladder or ovary, 2. Planned to start a (new) course of chemotherapy with a minimum intent of 3 months therapy, 3. With signed informed consent. Note: Chemotherapy is defined as any conventional cytotoxic treatment. Biological agents used alone are not considered as chemotherapy but could be associated with cytotoxic agents. 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion criteria related to study methodology: 1. Legal lower age limitations (country specific) 2. Life expectancy less than 3 months 3. ECOG (Eastern Cooperative Oncology Group) Performance status of 3 or 4 4. Calculated creatinine clearance 180 mm Hg or diastolic blood pressure > 110 mm Hg) - Hemorrhagic stroke or recent (in the last 3 months) brain, spinal or ophthalmic surgery - Known cerebral hemorrhagic lesion - Primary or metastatic tumor which is at high bleeding-risk according to investigator’s judgment - Known structural damage or other pathologic process involving the central nervous system (brain metastases, vascular malformation…) - Thrombocytopenia (platelet count 1.5 ULN or International Normalized ratio (INR) >1.5. 7. Any treatment with other anti-thrombotic agents within 2 weeks prior to randomization or planned during the study treatment period such as: - Parenteral anticoagulants (UFH, LMWH: enoxaparin, dalteparin, nadroparin..., or other agents such as fondaparinux, bivalirudin, hirudin) - Oral anticoagulants (Vitamin K antagonists) - Anti-GPIIb/IIIa: eptifibatide, tirofiban, abciximab - Thrombolytic agents Note: Chronic treatment with anti-platelet agents such as low dose of aspirin (up to 325 mg/day) or clopidogrel or ticlopidine in patients with coronary artery disease is allowed - To maintain patency of central venous catheter, saline flushing solutions are highly recommended. However, if it is local practice, flushing solutions with small amounts of heparin (max 500 units) are allowed. - Should an occlusion of the CVC occur, it is advised an attempt to restore the CVC patency by infusion of urokinase 5000-10000 units (could be repeated up to a dose of 50 000 units) or alteplase 2 mg. 8. Subject who requires a systematic venous thromboprophylaxis with anticoagulant or a curative anti-coagulant or thrombolytic treatment 9. Pelvic venous obstruction or superior vena cava syndrome 10. Subject unlikely to comply with protocol, e.g., uncooperative attitude, inability to return for follow-up visits, inability to receive daily injection (self-injection or by relative of patient or by Health care professional) and unlikelihood of completing the study 11. Treatment with any investigational product or investigational device in the last 30 days or 5 half lives (whichever is longer) prior to randomization 12. Any previous exposure to AVE5026 (e.g.: participation in any previous AVE5026 clinical trial) Note: A patient could not be randomized in the study more than once Exclusion criteria related to AVE5026: 13. History of heparin-induced thrombocytopenia 14. Known hypersensitivity to UFH or LMWH 15. Pregnant or nursing woman or women of childbearing potential not protected by highly effective contraceptive method of birth control as defined for contraception in the Informed Consent Form and/or in a local protocol addendum for the duration o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: To evaluate the safety of AVE5026 in cancer patients at high risk for VTE and who are undergoing chemotherapy, to document AVE5026 exposures, to try identifying a metagene predictor of VTE and to assess the survival status at one year in this population.;Primary end point(s): The primary efficacy endpoint is the time-to-first occurrence of any component of the composite endpoint of the following documented outcome results, confirmed by a blinded Adjudication Committee, occurring from randomization up to 3 calendar days after last study drug injection: - Any symptomatic DVT of the lower limbs - Any symptomatic DVT of the upper limbs (including CVC-related thrombosis) - Any non fatal PE - VTE-related deaths (fatal PE or unexplained deaths) Other efficacy outcomes include each component of the primary efficacy endpoint, from randomization up to 3 calendar days after last study drug and the initiation of curative anticoagulant or thrombolytic treatment by the investigator after local VTE assessment. Safety parameters include bleedings (major and clinically relevant non-major as classified by a blinded adjudication committee), transfusions requirements, hemoglobin, platelet count, liver and renal laboratory data, serious or non-serious adverse events and deaths (classified as VTE-related, fatal bleeding or other by a blinded Adjudication Committee) up to 3 calendar days after last IP injection and up to the follow-up visit Pharmacokinetics 4 blood samples per patient will be drawn in all patients from selected centers to document the AVE5026 exposures in this population . Genomics 1 blood sample per patient will be drawn to identify a metagene predictor of VTE in patients who gave informed consent to participate in this substudy. ;Main Objective: To compare the efficacy of once daily (q.d.) subcutaneous (s.c.) injections of 20 mg AVE5026 with placebo in the prevention of venous thromboembolism (VTE) in cancer patients at high risk for VTE and wh | — |
Countries
Austria, Belgium, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Hungary, Italy, Latvia, Lithuania, Netherlands, Portugal, Slovenia, Spain, Sweden, United Kingdom
Outcome results
None listed