Enoxaparin Low Molecular Weight Heparin (LMWH) in Advanced Non Small Cell Lung Cancer: Effect on Survival and Symptom Control in Patients Undergoing First Line Chemotherapy (SYRINGES)

Study Overview
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Brief Summary
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Rationale: a number of recent phase III randomized trials have shown a survival benefit of a treatment with subcutaneous low-molecular weight heparin in patients with advanced solid malignancies. The survival advantages observed in the studies persist for months after the active treatment with LMWHs. Therefore these survival advantages are thought to be due to effects of LMWHs on tumor cell biology. First line treatment of advanced NSCLC patients with the Cisplatin + Docetaxel combination has been widely studied, and is amongst the most active treatments currently available. The occurrence of grade 3/4 thrombopenia in several phase III trials was in the 0-3% range, making it an ideal chemotherapy regimen to combine with LMWHs in the treatment of advanced NSCLC.

Detailed Description
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Purpose: the aim of this study is to evaluate the potential beneficial antitumoral effect of LMWH enoxaparin in patients with locally advanced or metastatic NSCLC determined by the time to progression, the overall survival and the symptom control. LMWH will be added to a first line cisplatin-based chemotherapy.

Official Title
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Low Molecular Weight Heparin in Advanced Non Small Cell Lung Cancer (NSCLC): a Randomized Open Label Phase III Study Evaluating the Effect of Enoxaparin (Clexane) on Survival and Symptom Control in Patients With Stage IIIB and IV NSCLC Undergoing a Cisplatin Based First Line Chemotherapy: the SYRINGES Trial

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: cisplatin + docetaxel
* Drug: cisplatin + docetaxel + enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Locally advanced or metastatic NSCLC (stage IIIB or IV) Patients who are not candidates for radical combined modality treatments or high-dose radiation therapy At least one measurable lesion according to RECIST criteria Good performance status Adequate haematological, renal and liver function Written informed consent Exclusion Criteria: Previous chemotherapy for NSCLC Brain metastasis History of cerebral haemorrhage, neurosurgery within 3 previous months or surgery within the past 6 months Indication for anticoagulant therapy, thrombolytic therapy or antiplatelet therapy for cardiovascular disease Concomitant therapy with an anti-angiogenesis agent Contra-indication for LMWH Life expectancy of < 3 months Serious concomitant systemic disease, uncontrolled arterial hypertension, active peptic ulcer or other condition which does not permit study treatment or follow-up required to comply with the study protocol

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm A<br>Chemotherapy without LMWH | Drug: cisplatin + docetaxel<br>* docetaxel 75 mg/m2 d1 and cisplatin 75mg/m2 d1 (q 3wks for 4 cycles)<br>* Other names: Taxotere;|
| Experimental: Arm B<br>Chemotherapy with LMWH | Drug: cisplatin + docetaxel + enoxaparin<br>* cisplatin 75 mg/m2 d1 and docetaxel 75 mg/m2 d1 (q 3 wks for 4 cycles) + daily enoxaparin 1mg/kg/d sc<br>* Other names: LMWH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival |  | during chemotherapy and follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptom control evaluated with the Lung Cancer Symptoms Scale (LCSS) |  | during chemotherapy and follow-up | 
| Overall Survival |  | during chemotherapy and follow-up | 
| Best Overall Response |  | during chemotherapy and follow-up | 
| Incidence of total documented thromboembolic and hemorrhagic events |  | during chemotherapy and follow-up | 
| Overall safety and tolerability |  | during chemotherapy and follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-Small Cell Lung Cancer, chemotherapy, Low Molecular Weight Heparin