Prevention of Venous and Arterial Thromboembolism, in Cancer Patients Undergoing Chemotherapy, With a Low Molecular Weight Heparin (Nadroparin Calcium)

Study Overview
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Brief Summary
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In this phase III, multicenter study, 1200 patients with lung, breast, gastrointestinal (stomach, colon-rectum, pancreas), ovarian or head and neck cancer undergoing chemotherapy will be randomly assigned (at the beginning of cytotoxic therapy) in a 2:1 ratio and in double-blind conditions to a treatment with subcutaneous low molecular weight heparin (nadroparin calcium, one injection/day) or placebo for the overall duration of chemotherapy or up to a maximum of 4 months (+/- 10 days).

Official Title
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Prevention of Venous and Arterial Thromboembolism, in Cancer Patients Undergoing Chemotherapy, With a Low Molecular Weight Heparin (Nadroparin Calcium). A Randomized, Placebo-controlled, Double-blind, Multicenter Phase III Study.

Conditions
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Advanced Cancer, Metastatic Cancer

Intervention / Treatment
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* Drug: Nadroparin calcium
* Drug: saline solution (placebo)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: both sexes;aged>18 years; suffering from different types of malignancies(lung, breast,gastric,colon- rectum,pancreatic,ovarian,head and neck cancer)undergoing systemic chemotherapy, having signed Informed Consent prior to initiation of any study procedure. EXCLUSION CRITERIA: adjuvant and neo-adjuvant chemotherapy; objectively confirmed venous or arterial thromboembolism in the last three months; antithrombotic treatment for other indications; life expectancy of less than 3 months; Performance Status>2(ECOG); active bleeding or bleedings in the last four weeks requiring hospitalization,transfusion or surgical intervention; bleeding diathesis(prothrombin time<70% or activated partial thromboplastin time ratio>1.3),or platelet count<50x10^9/L; cerebrovascular hemorrhage in the last six months; known active gastric or duodenal ulcer; known cerebral metastasis; cerebral aneurysm; III-IV grade diabetic retinopathy; severe and uncontrolled hypertension(systolic blood pressure>180 mmHg or diastolic blood pressure>110 mmHg); chronic atrial fibrillation; acute endocarditis; acute pancreatitis; known hypersensitivity to unfractionated heparin or LMWH; previous occurrence of heparin-induced thrombocytopenia; renal impairment (dependent on dialysis or creatinine higher than 2.5mg%); liver insufficiency (alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase levels>3 times the upper limit of the normal ranges and/or total bilirubin >3.0 mg/ml); pregnancy or childbearing potential without adequate contraception; treatment with other investigational drugs or patient inclusion in other clinical trials; patients who are unable to fulfill the study requirements in terms of visits/compliance to treatment.

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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: saline solution<br>Pre-filled syringes of 0.4 ml, 1 subcutaneous injection/day (every 24 hours). | Drug: saline solution (placebo)<br>* Pre-filled syringes of 0.4 ml , 1 subcutaneous injection/day (every 24 hours).<br>|
| Experimental: nadroparin calcium<br>Nadroparin calcium; Pre-filled syringes of 0.4 ml (3.800 anti-Xa IU), 1 subcutaneous injection/day (every 24 hours). | Drug: Nadroparin calcium<br>* Nadroparin calcium; Pre-filled syringes of 0.4 ml (3.800 anti-Xa IU), 1 subcutaneous injection/day (every 24 hours).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of symptomatic venous and arterial thromboembolism, in patients with metastatic or locally advanced solid tumors undergoing chemotherapy |  | Events occurring during the four months of treatment plus 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival, at the end of study treatment |  | Events occurring during the four months of treatment plus 10 days | 
| Response to chemotherapy |  | Events occurring during the four months of treatment plus 10 days | 
| For patients with central venous catheters (CVC), complications of possible thrombotic origin, such as malfunction or requirement of CVC removal |  | Events occurring during the four months of treatment plus 10 days | 
| Superficial thrombophlebitis of lower limbs |  | Events occurring during the four months of treatment plus 10 days | 
| Asymptomatic thromboembolic events diagnosed during tests performed for other purposes |  | Events occurring during the four months of treatment plus 10 days | 
| Safety (major bleeding, minor bleeding, other adverse events) |  | Events occurring during the four months of treatment plus 48 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thromboembolism, cancer, chemotherapy, low-molecular-weight-heparin, nadroparin