Clinical trial NCT00519805: Dalteparin in Preventing Blood Clots in Patients With Lung Cancer
Official title: FRAGMATIC - A Randomised Phase III Clinical Trial Investigating the Effect of FRAGMin Added to Standard Therapy In Patients With Lung Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Lung Cancer
Thromboembolism
Keywords: thromboembolism
extensive stage small cell lung cancer
limited stage small cell lung cancer
stage IV non-small cell lung cancer
stage II non-small cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage I non-small cell lung cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-08-23
Enrollment: 2200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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®)

Primary outcomes:
measure: Overall survival
Secondary outcomes:
measure: Venous thrombotic event-free survival
measure: Serious adverse events
measure: Metastasis-free survival
measure: Toxicity
measure: Quality of life as measured by EQ-5D
measure: Breathlessness (dyspnea) as measured by the Cancer Dyspnea Scale
measure: Anxiety and depression as measured by the Hospital Anxiety and Depression Scale
measure: Cost effectiveness
measure: Cost utility
Other outcomes:
Locations:
city: Aylesbury-Buckinghamshire
country: United Kingdom
facility: Stoke Mandeville Hospital
state: England
city: Barrow in Furness
country: United Kingdom
facility: Furness General Hospital
state: England
city: Blackburn
country: United Kingdom
facility: Royal Blackburn Hospital
state: England
city: Blackpool
country: United Kingdom
facility: Blackpool Victoria Hospital
state: England
city: Bournemouth
country: United Kingdom
facility: Royal Bournemouth Hospital
state: England
city: Bristol
country: United Kingdom
facility: Bristol Haematology and Oncology Centre
state: England
city: Burnley
country: United Kingdom
facility: Burnley General Hospital
state: England
city: Burton-upon-Trent
country: United Kingdom
facility: Queen's Hospital
state: England
city: Bury St. Edmunds
country: United Kingdom
facility: West Suffolk Hospital
state: England
city: Coventry
country: United Kingdom
facility: Walsgrave Hospital
state: England
city: Darlington
country: United Kingdom
facility: Darlington Memorial
state: England
city: Derby
country: United Kingdom
facility: Derbyshire Royal Infirmary
state: England
city: Doncaster
country: United Kingdom
facility: Doncaster Royal Infirmary
state: England
city: Dorchester
country: United Kingdom
facility: Dorset County Hospital
state: England
city: Dudley
country: United Kingdom
facility: Russells Hall Hospital
state: England
city: Gateshead
country: United Kingdom
facility: Queen Elizabeth Hospital
state: England
city: High Wycombe
country: United Kingdom
facility: Wycombe General Hospital
state: England
city: Kidderminster Worcestershire
country: United Kingdom
facility: Kidderminster Hospital
state: England
city: Lancaster
country: United Kingdom
facility: Royal Lancaster Infirmary
state: England
city: London
country: United Kingdom
facility: Whipps Cross Hospital
state: England
city: London
country: United Kingdom
facility: Saint Bartholomew's Hospital
state: England
city: London
country: United Kingdom
facility: Helen Rollason Cancer Care Centre at North Middlesex Hospital
state: England
city: London
country: United Kingdom
facility: Whittington Hospital
state: England
city: London
country: United Kingdom
facility: University College Hospital
state: England
city: London
country: United Kingdom
facility: UCL Cancer Institute
state: England
city: Luton
country: United Kingdom
facility: Luton and Dunstable Hospital
state: England
city: Middlesbrough
country: United Kingdom
facility: James Cook University Hospital
state: England
city: Milton Keynes
country: United Kingdom
facility: Milton Keynes General Hospital
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Newcastle Upon Tyne Hospitals NHS Trust
state: England
city: Norfolk
country: United Kingdom
facility: James Paget Hospital
state: England
city: North Shields
country: United Kingdom
facility: North Tyneside Hospital
state: England
city: North Yorkshire
country: United Kingdom
facility: Friarage Hospital
state: England
city: Northampton
country: United Kingdom
facility: Northampton General Hospital
state: England
city: Northwood
country: United Kingdom
facility: Mount Vernon Cancer Centre at Mount Vernon Hospital
state: England
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: England
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
state: England
city: Nuneaton
country: United Kingdom
facility: George Eliot Hospital
state: England
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: England
city: Poole Dorset
country: United Kingdom
facility: Dorset Cancer Centre
state: England
city: Preston
country: United Kingdom
facility: Rosemere Cancer Centre at Royal Preston Hospital
state: England
city: Reading
country: United Kingdom
facility: Berkshire Cancer Centre at Royal Berkshire Hospital
state: England
city: Redditch, Worcestershire
country: United Kingdom
facility: Alexandra Healthcare NHS
state: England
city: Scarborough
country: United Kingdom
facility: Scarborough General Hospital
state: England
city: Sheffield
country: United Kingdom
facility: Cancer Research Centre at Weston Park Hospital
state: England
city: Slough, Berkshire
country: United Kingdom
facility: Wexham Park Hospital
state: England
city: South Shields
country: United Kingdom
facility: South Tyneside District Hospital
state: England
city: Stafford
country: United Kingdom
facility: Staffordshire General Hospital
state: England
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Warwick, Warwickshire
country: United Kingdom
facility: South Warwickshire Hospital
state: England
city: Weston-super-Mare
country: United Kingdom
facility: Weston General Hospital
state: England
city: Wolverhampton
country: United Kingdom
facility: New Cross Hospital
state: England
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
state: England
city: Bangor
country: United Kingdom
facility: Ysbyty Gwynedd
state: Wales
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
city: Llandough
country: United Kingdom
facility: Llandough Hospital
state: Wales
city: Llantrisant
country: United Kingdom
facility: Royal Glamorgan Hospital
state: Wales
city: Mid Glamorgan
country: United Kingdom
facility: Prince Charles Hospital
state: Wales
city: Newport Gwent
country: United Kingdom
facility: Royal Gwent Hospital
state: Wales
city: Rhyl, Denbighshire
country: United Kingdom
facility: Glan Clwyd Hospital
state: Wales
Study officials:
affiliation: Velindre NHS Trust
name: Fergus Macbeth, MD
role: STUDY_CHAIR
References:
citation: Griffiths GO, Burns S, Noble SI, Macbeth FR, Cohen D, Maughan TS. FRAGMATIC: a randomised phase III clinical trial investigating the effect of fragmin added to standard therapy in patients with lung cancer. BMC Cancer. 2009 Oct 6;9:355. doi: 10.1186/1471-2407-9-355.
citation: Rutjes AW, Porreca E, Candeloro M, Valeriani E, Di Nisio M. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev. 2020 Dec 18;12(12):CD008500. doi: 10.1002/14651858.CD008500.pub5.