Effect of Low Molecular Weight Heparin: Tinzaparin in Lung Tumours (TILT)

Phase 3

Completed

• Conditions: Non Small Cell Lung Cancer; Lung Cancer
• Interventions: Drug: Tinzaparin sodium 100 UI/Kg/OD for 12 weeks

• Registration Number: NCT00475098
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Experiments suggest that low molecular weight heparin (LMWH) inhibits tumor growth and metastasis. Studies in humans suggest that LMWH is associated with a higher survival in patients with cancer related thrombosis. Two recent studies suggest that LMWH may increase the survival of patients with cancer who do not have an associated thrombosis. The purpose of the study is to assess the effect of LMWH on the overall survival of patients with localized non-small cell lung cancer after complete surgical resection.

Detailed Description

Phase III, prospective, multicentric, randomized, controlled, open trial in parallel groups with a blind adjudication of all end-point criteria.

Reference therapy :

Patients randomized to the control group will receive postoperative treatment according to local practice in the participating centers. However, the participating centers will have to comply with the following guidelines.

Adjuvant chemotherapy:

Adjuvant chemotherapy will be offered in all patients with stage II and stage IIIA cancers. Adjuvant chemotherapy will be platin based and include two drugs for a maximum of 4 cycles. Each center will have to select one regimen before the beginning of the study for all patients included in the study.

Preoperative chemotherapy:

Patients who had chemotherapy before surgery can be included in the study provided that they had a complete surgical resection. In this case the tumor stage for stratification will be the pathologic stage assessed after surgery.

Stage I cancers:

Patients with stage I cancer who will not be selected for postoperative chemotherapy can be included in the study. Contraindication to chemotherapy Patients with a contraindication to postoperative chemotherapy and those who refuse chemotherapy can be included in the study provided they fulfill all inclusion and exclusion criteria.

Experimental treatment:

Experimental treatment is tinzaparin administered subcutaneously once a day at the dose of 100 IU/Kg during a twelve week period beginning after a maximum period of 8 weeks after surgery. Patients randomized in the experimental group will receive adjuvant postoperative treatment according to local practice with the same guidelines as in the control group.

* Patient follow-up:

All patients will be followed according to local practice, but at least two outpatient visits with a chest radiograph will be planned each year during the three year follow-up period after last inclusion.

* Duration of the trial:

Inclusion period (first patient in to last patient in) : 6 years. Patient total follow-up (from surgery to end of follow-up) : 3 years after last inclusion (first enrolled patients were followed 9 years). Total study period : 9 years.

Study Timeline

• Study First Submitted: 2007-05-16
• Study First Submitted QC: 2007-05-16
• Study First Posted: 2007-05-17
• Study Start: 2007-06
• Status Verified: 2016-08
• Primary Completion: 2016-08
• Study Completion: 2016-08
• Last Update Submitted: 2016-09-01
• Last Update Posted: 2016-09-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 553

Inclusion Criteria

Patients with completely resected non-small cell lung cancer of stage I, II, or IIIA T3N1 confirmed by histology can be included in the study Patients who had preoperative chemotherapy, those who are selected for adjuvant chemotherapy and those who are not candidates for adjuvant chemotherapy (because they have a contraindication to chemotherapy or they have a stage I cancer) are eligible for the study Written informed consent age > 18 years

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Exclusion Criteria

Previous heparin induced thrombocytopenia Allergy to tinzaparin Allergy to sulfites Renal failure with a creatinin clearance < 30 ml/min according to COCKROFT formula Prothrombin time < 50% Platelet count < 100 G/L Increased bleeding risk: ongoing hemorrhage, major bleeding within 10 days, previous intracerebral bleeding, uncontrolled hypertension (SAP > 180 mmHg or DAP > 120 mmHg) Indication for curative anticoagulant treatment on inclusion More than 6 weeks between surgery and inclusion Known pregnancy or no efficient contraception for women of childbearing age Breast feeding Previous malignant disease diagnosed within 2 years except in situ carcinoma of the uterine cervix or spinal-cellular or baso-cellular cutaneous carcinoma Inclusion in another therapeutic trial at the time of inclusion Treatment with an experimental drug within 30 days before inclusion in the study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A	Tinzaparin sodium 100 UI/Kg/OD for 12 weeks	-
B	Tinzaparin sodium 100 UI/Kg/OD for 12 weeks	-

Primary Outcome Measures

Name	Time	Method
Overall 3-year mortality	overall 3-years	The first included patients will be followed 9 years with no impact on the total duration of the study.

Secondary Outcome Measures

Name	Time	Method
Symptomatic venous thromboembolic events	Overall five year survival	Symptomatic venous thromboembolic events of the first enrolled patients will be assessed 9 years after inclusion
Major bleeding time	Overall five year survival	Disease free survival of the first enrolled patients will be assessed 9 years after inclusion
Disease free survival	Overall five year survival	Disease free survival of the first enrolled patients will be assessed 9 years after inclusion
Cancer related mortality	Overall five year survival	Cancer related mortality of the first enrolled patients will be assessed 9 years after inclusion

Trial Locations

Locations (1)

Hopital Européen Georges Pompidou; 🇫🇷 Paris, France