Dalteparin in Preventing Blood Clots in Patients With Lung Cancer

FRAGMATIC - A Randomised Phase III Clinical Trial Investigating the Effect of FRAGMin Added to Standard Therapy In Patients With Lung Cancer

RATIONALE: Anticoagulants, such as dalteparin, may help prevent blood clots from forming in patients with lung cancer. It is not yet known whether dalteparin is effective in preventing blood clots in patients with lung cancer.

PURPOSE: This randomized phase III trial is studying how well dalteparin works in preventing blood clots in patients with lung cancer.

OBJECTIVES:

Primary

• Determine whether the addition of dalteparin results in improved survival.

Secondary

• Determine venous thrombotic event-free survival and metastasis-free survival.
• Determine serious adverse events in patients treated with this drug.
• Determine the toxicity of this drug in these patients.
• Determine the quality of life, breathlessness, anxiety, and depression in patients treated with this drug.
• Determine the cost effectiveness and cost utility of this drug.

OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.

• Arm I (control): Patients receive anticancer treatment considered appropriate by the local medical team.
• Arm II: Patients receive anticancer treatment considered appropriate by the local medical team. Beginning before the start of the first definitive anticancer treatment, patients receive dalteparin subcutaneously daily for up to 24 weeks.

Quality of life, anxiety, depression, and dyspnea are assessed at baseline, at 12 and 24 weeks, and then at 9 and 12 months.

After completion of therapy, patients are followed at 9 months, 1 year, and then every 6 months for at least 2 years.

DISEASE CHARACTERISTICS:

• Histopathological or cytological diagnosis of primary bronchial carcinoma (small cell or non-small cell lung cancer) within the past 6 weeks
• No other intrathoracic tumors (e.g., carcinoid tumor, mesothelioma, lymphoma, or lung metastases from another primary site)
• No clinically apparent brain metastases

PATIENT CHARACTERISTICS:

• ECOG performance status 0-3
• Platelet count ≥ 100,000/mm³
• Serum creatinine ≤ 150 µmol/L
• Willing and able to self-administer dalteparin by daily subcutaneous injection or have it administered by a caregiver
• Not pregnant or nursing
• Fertile female patients must use effective contraception (if sexually active)
• No hemorrhagic stroke within the past 3 months
• No known bleeding disorder
• No hemoptysis of CTC ≥ grade 2 (i.e., symptomatic hemoptysis requiring medical intervention)
• No central venous catheter requiring the use of thromboprophylaxis
• No known hypersensitivity to dalteparin, heparin, or other low molecular weight heparins (e.g., history of confirmed or suspected immunologically mediated heparin-induced thrombocytopenia; acute gastroduodenal ulcer; or subacute endocarditis)
• No prior illness likely to interfere with study treatment or comparisons

PRIOR CONCURRENT THERAPY:

• No prior treatment likely to interfere with study treatment or comparisons
• More than 12 months since prior and no concurrent therapeutic anticoagulation
• No concurrent ketorolac (Toradol®)