Evaluation of AVE5026 in the Prevention of Venous Thromboembolism in Cancer Patients Undergoing Chemotherapy

Study Overview
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Brief Summary
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The primary objective was to compare the efficacy of once daily subcutaneous injections of Semuloparin sodium (AVE5026) with placebo in the prevention of venous thromboembolism [VTE] in cancer patients at high risk for VTE and who were undergoing chemotherapy. The secondary objectives were to evaluate the safety of Semuloparin sodium (AVE5026), to document Semuloparin sodium (AVE5026) exposures, to try identifying a metagene predictor of VTE and to assess the survival status at one year in this population.

Detailed Description
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Randomization had to take place just prior to the first study drug injection (randomization ratio 1:1). The study period per participant was variable depending on the duration of chemotherapy. It included: a screening period up to 3 weeks, a double-blind treatment period, a follow-up period of 1 month. Study end date was at the latest 7 months following the randomization of the last participant (6 months treatment and 1 month follow-up).

Official Title
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A Multinational, Randomized, Double Blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AVE5026 in the Prevention of Venous Thromboembolism (VTE) in Cancer Patients at High Risk for VTE and Who Are Undergoing Chemotherapy

Conditions
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Venous Thromboembolism, Cancer

Intervention / Treatment
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* Drug: Semuloparin sodium
* Drug: Placebo (for semuloparin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Cancer patient with metastatic or locally advanced solid tumor of lung, pancreas, stomach, colon/rectum, bladder or ovary initiating a (new) course of chemotherapy with a minimum intent of 3 months therapy Exclusion Criteria: Required systematic venous thromboprophylaxis or curative treatment with anti-coagulant or thrombolytic; High risk of bleeding; Severe renal impairment (estimated creatinine clearance <30 mL/min); ECOG (Eastern Cooperative Oncology Group) performance status 3 & 4; Major surgery within 4 weeks before randomization; Known hypersensitivity to unfractionated heparin [UFH] or low molecular weight heparin [LMWH]. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semuloparin<br>Semuloparin sodium 20 mg once daily until change in chemotherapy regimen | Drug: Semuloparin sodium<br>* 0.4 mL solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection<br>* Other names: AVE5026;|
| Placebo Comparator: Placebo<br>Placebo (for semuloparin) once daily until change in chemotherapy regimen | Drug: Placebo (for semuloparin)<br>* 0.4 mL solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance but without active component Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or VTE-related Death | VTE included any symptomatic Deep Vein Thrombosis [DVT] of lower or upper limbs and any non-fatal Pulmonary Embolism [PE] as confirmed by a Central Independent Adjudication Committee [CIAC] after review of compression ultrasound or venography for DVT, ventilation/perfusion lung scan, pulmonary angiogram or spiral computer tomography lung scan for PE. VTE-related death included fatal PE and unexplained deaths without confirmatory autopsy. Any sudden death could be classified as fatal PE by the CIAC unless diagnostic test results strongly indicated an alternative diagnosis. | From randomization up to 3 days after last study drug injection | 
| Time-to-first Occurrence of VTE or VTE-related Death (Cumulative Incidence Function) | Participants alive and not having experienced VTE were right censored at last study drug injection plus 3 days. In order to correct for competing risks (Deaths other than VTE-related death), a model of cause-specific hazards was used to estimate the Cumulative incidence Function with Prentice non-parametric estimator. | From randomization up to 3 days after last study drug injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants who required the initiation of curative anticoagulant or thrombolytic treatment after VTE assessment | Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment was defined from investigator's answer to the question was the subject treated for VTE? asked after diagnostic tests for suspected VTE and after lung imaging test for tumor evaluation. | From randomization up to 3 days after last study drug injection | 
| Percentage of Participants Who Experienced Clinically Relevant Bleedings | Clinically Relevant Bleedings included overt bleedings classified by the CIAC as: major (fatal, in a critical area/organ, causing a drop in hemoglobin ≥2 g/dL or requiring transfusion ≥2 units of blood) clinically relevant non-major (requiring medical intervention and not meeting criteria for major bleeding). | From first study drug injection up to 3 days after last study drug injection | 
| Overall survival [OS] | Survival status was collected for all participants either one year after randomization, or at the study end date, (ie, 7 months following randomization of the last patient), whichever came first. OS was defined as the time from date of randomization to date of death due to any cause. Participants alive were censored at last date of contact that they were known to be alive. | From randomization up to 1 year after randomization or 7 months following randomization of the last participant, whichever came first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chemotherapy